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1.
Sci Rep ; 12(1): 7581, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35534522

RESUMO

The epidemiological association between exposure to particulate matter (PM10) and various respiratory and cardiovascular problems is well known, but the mechanisms driving these effects remain unclear. Neutrophils play an essential role in immune defense against foreign agents and also participate in the development of inflammatory responses. However, the role of these cells in the PM10 induced inflammatory response is not yet fully established. Thus, this study aims to evaluate the effect of PM10 on the neutrophil-mediated inflammatory response. For this, neutrophils from healthy adult human donors were in vitro exposed to different concentrations of PM10. The cell viability and cytotoxic activity were evaluated by MTT. LDH, propidium iodide and reactive oxygen species (ROS) were quantified by flow cytometry. Interleukin 8 (IL-8) expression, peptidyl arginine deiminase 4 (PAD4), myeloperoxidase (MPO), and neutrophil elastase (NE) expression were measured by RT-PCR. IL-8 was also quantified by ELISA. Fluorescence microscopy was used to evaluate neutrophil extracellular traps (NETs) release. The in vivo inflammatory responses were assessed in BALB/c mice exposed to PM10 by histopathology and RT-PCR. The analysis shows that PM10 exposure induced a cytotoxic effect on neutrophils, evidenced by necrosis and LDH release at high PM10 concentrations. ROS production, IL-8, MPO, NE expression, and NETs release were increased at all PM10 concentrations assessed. Neutrophil infiltration in bronchoalveolar lavage fluid (BALF), histopathological changes with inflammatory cell infiltration, and CXCL1 expression were observed in PM10-treated mice. The results suggest that lung inflammation in response to PM10 could be mediated by neutrophils activation. In this case, these cells migrate to the lungs and release pro-inflamatory mediators, including ROS, IL-8, and NETs. Thus, contributing to the exacerbation of respiratory pathologies, such as allergies, infectious and obstructive diseases.


Assuntos
Armadilhas Extracelulares , Neutrófilos , Animais , Modelos Animais de Doenças , Armadilhas Extracelulares/metabolismo , Humanos , Interleucina-8/metabolismo , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/metabolismo , Material Particulado/metabolismo , Material Particulado/toxicidade , Espécies Reativas de Oxigênio/metabolismo
2.
Med Sci Monit ; 28: e936065, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35535007

RESUMO

BACKGROUND Chemical pleurodesis is one of the major therapeutic options for patients with recurrent malignant pleural effusion. Mesothelial cells are considered to play a pivotal role in the response to different chemical compounds (sclerosants) used for pleurodesis. Malignant cells might have an impact on the mesothelial response to applied sclerosing agents and, in consequence, on the efficacy of pleurodesis. We aimed to evaluate the impact of cancer cell paracrine on mesothelial cell response to different sclerosing agents. MATERIAL AND METHODS The study used mesothelial cell (MeT-5A) cultures stimulated with sclerosing agents (talc, doxycycline, iodopovidone, and TGF-ß for 24 h) in the presence or absence of supernatants from adenocarcinoma cultures (HCC827). The mesothelial mRNA expression and protein levels of IL-6, IL-8, and TGF-ß was assessed. Further, lung fibroblasts were cultured with and without cell supernatants from previously established cell cultures for 24 h. Then, concentration of soluble collagen was evaluated in culture supernatants. RESULTS The exposure of mesothelial cells to sclerosants decreased the concentration of IL-6 and IL-8 protein. The addition of mediators secreted by adenocarcinoma altered the inflammatory response of the mesothelial cells to sclerosing agents. IL-8 concentration in cultures stimulated with talc and adenocarcinoma supernatant was higher compared to cultures stimulated with talc only. The exposure of lung fibroblasts to supernatant from mesothelial cell (with or without adenocarcinoma) did not affect collagen secretion. CONCLUSIONS An addition of soluble factors produced by adenocarcinoma altered the inflammatory response of the pleural mesothelial cells after stimulation with sclerosing agents. Our observations suggest that the tumor paracrine effect affects biological pathways of pleurodesis.


Assuntos
Adenocarcinoma , Derrame Pleural Maligno , Adenocarcinoma/patologia , Colágeno/metabolismo , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Pleura/patologia , Soluções Esclerosantes , Talco/metabolismo , Talco/farmacologia , Talco/uso terapêutico
3.
Comput Math Methods Med ; 2022: 4634925, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35509853

RESUMO

Objective: miR-141-3p has been demonstrated to be both anti-inflammatory and osteoprotective. This study is aimed at investigating the effect of miR-141-3p on osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) stimulated by Porphyromonas gingivalis lipopolysaccharide (PgLPS) and its mechanism. Methods: PgLPS was used to induce an inflammatory environment, and overexpression of miR-141-3p was done to assess its effect on hPDLSCs in an inflammatory environment. The level of miR-141-3p and EZH2 in hPDLSCs from each treatment group was detected via qRT-PCR, and the inflammatory factors IL-6 and IL-8 in the supernatant of each group were detected by ELISA. ALP staining and alizarin red staining were used to assess the effect of miR-141-3p on the osteogenic differentiation ability of hPDLSCs, and also, western blot was used to detect expression of osteogenic differentiation-related proteins. Further, dual-luciferase reporter assay examined whether miR-141-3p targeted EZH2. Results: PgLPS led to a significant decrease of miR-141-3p in hPDLSCs. Overexpression of miR-141-3p could enhance ALP activity and alizarin red staining intensity and increase Runx2, OPN and OCN protein expression levels in PgLPS-treated hPDLSCs. Additionally, miR-141-3p could reduce IL-6 and IL-8. miR-141-3p could target and negatively regulate EZH2, and overexpression of EZH2 reversed the promoting effect of miR-141-3p on osteogenic differentiation. Conclusion: miR-141-3p can attenuate PgLPS-induced inhibition of osteogenic differentiation and inflammation in hPDLSCs by negatively regulating EZH2.


Assuntos
MicroRNAs , Ligamento Periodontal , Diferenciação Celular , Células Cultivadas , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/farmacologia , Humanos , Inflamação/genética , Inflamação/metabolismo , Interleucina-6/genética , Interleucina-8/genética , Interleucina-8/metabolismo , Interleucina-8/farmacologia , Lipopolissacarídeos , MicroRNAs/genética , MicroRNAs/metabolismo , Osteogênese , Porphyromonas gingivalis/metabolismo , Células-Tronco/metabolismo
4.
Front Immunol ; 13: 863309, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35514973

RESUMO

Cardiac fibroblasts participate in the inflammatory process of heart diseases as sentinel cells of the cardiac tissue. In this study, we investigated the effect of the proinflammatory cytokine, interleukin 1ß (IL-1ß), on the expression of interleukin 8 (IL-8), which contributes to the induction of innate immunity via the activation and recruitment of innate immune cells, such as neutrophils, to the site of inflammation in canine cardiac fibroblasts. IL-1ß mediates IL-8 mRNA expression and protein release in a dose- and time-dependent manner. The IL-ß-mediated IL-8 protein release and mRNA expression were inhibited by 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide, an inhibitor of the transcription factor, nuclear factor (NF)-κB. In cells treated with IL-1ß, NF-κB p65 and p105 were transiently phosphorylated, indicating the activation of NF-κB. However, IL-1ß failed to induce IL-8 mRNA expression in the cells transfected with p65 small interfering RNA (siRNA), but not in those transfected with p105 siRNA. These observations suggest that IL-1ß induces IL-8 expression via the activation of NF-κB p65 in canine cardiac fibroblasts.


Assuntos
Interleucina-8 , NF-kappa B , Animais , Cães , Fibroblastos/metabolismo , Interleucina-1beta/metabolismo , Interleucina-8/metabolismo , NF-kappa B/metabolismo , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo
5.
Bioengineered ; 13(5): 11361-11372, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35506423

RESUMO

Helicobacter pylori (H.pylori) infection caused by gastric mucosal inflammation plays a pivotal role in the progression of gastric diseases. The recruitment and attachment of monocytes to the gastric mucosal epithelium are a major event in the early stages of H. pylori-associated gastric diseases. Everolimus is a mechanistic/mammalian target of rapamycin (mTOR) inhibitor used to prevent tumor growth by inhibiting the PI3K signaling pathway. Here, we examined the pharmacological role of Everolimus against H.pylori-induced damage in gastric epithelial cells. Firstly, we found that Everolimus ameliorated H.pylori-induced oxidative stress by reducing reactive oxygen species (ROS) and malondialdehyde (MDA). Secondly, Everolimus significantly reduced the expressions of the pro-inflammatory cytokines interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-8. Moreover, it decreased the production of the pro-inflammatory chemokines C-X-C motif ligand 1 (CXCL1) and macrophage chemoattractant protein-1 (MCP-1). Importantly, Everolimus suppressed the induction of the adhesion molecule intracellular adhesion molecule-1 (ICAM-1) and the attachment of THP-1 monocytes to gastric epithelial AGS cells. Our data also shows that Everolimus inhibited the activation of the NF-κB signaling pathway. Therefore, we conclude that Everolimus could protect gastric epithelial cells by mitigating H.pylori-induced inflammatory response and the attachment of monocytes to epithelial cells.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Células Epiteliais/metabolismo , Everolimo/metabolismo , Everolimo/farmacologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/metabolismo , Helicobacter pylori/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-8/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo
6.
PLoS Pathog ; 18(4): e1010468, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35385545

RESUMO

An overreactive inflammatory response and coagulopathy are observed in patients with severe form of COVID-19. Since increased levels of D-dimer (DD) are associated with coagulopathy in COVID-19, we explored whether DD contributes to the aberrant cytokine responses. Here we show that treatment of healthy human monocytes with DD induced a dose dependent increase in production of pyrogenic mediator, Prostaglandin E2 (PGE2) and inflammatory cytokines, IL-6 and IL-8. The DD-induced PGE2 and inflammatory cytokines were enhanced significantly by co-treatment with immune complexes (IC) of SARS CoV-2 recombinant S protein or of pseudovirus containing SARS CoV-2 S protein (PVCoV-2) coated with spike-specific chimeric monoclonal antibody (MAb) containing mouse variable and human Fc regions. The production of PGE2 and cytokines in monocytes activated with DD and ICs was sensitive to the inhibitors of ß2 integrin and FcγRIIa, and to the inhibitors of calcium signaling, Mitogen-Activated Protein Kinase (MAPK) pathway, and tyrosine-protein kinase. Importantly, strong increase in PGE2 and in IL-6/IL-8/IL-1ß cytokines was observed in monocytes activated with DD in the presence of IC of PVCoV-2 coated with plasma from hospitalized COVID-19 patients but not from healthy donors. The IC of PVCoV-2 with convalescent plasma induced much lower levels of PGE2 and cytokines compared with plasma from hospitalized COVID-19 patients. PGE2 and IL-6/IL-8 cytokines produced in monocytes activated with plasma-containing IC, correlated well with the levels of spike binding antibodies and not with neutralizing antibody titers. Our study suggests that a combination of high levels of DD and high titers of spike-binding antibodies that can form IC with SARS CoV-2 viral particles might accelerate the inflammatory status of lung infiltrating monocytes leading to increased lung pathology in patients with severe form of COVID-19.


Assuntos
COVID-19 , Monócitos , Animais , Complexo Antígeno-Anticorpo , COVID-19/terapia , Citocinas/metabolismo , Dinoprostona/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio , Humanos , Imunização Passiva , Fatores Imunológicos/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Camundongos , Glicoproteína da Espícula de Coronavírus/metabolismo
7.
Int J Mol Sci ; 23(7)2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35409421

RESUMO

In the novel pandemic of Coronavirus Disease 2019, high levels of pro-inflammatory cytokines lead to endothelial activation and dysfunction, promoting a pro-coagulative state, thrombotic events, and microvasculature injuries. The aim of the present work was to investigate the effect of SARS-CoV-2 on pro-inflammatory cytokines, tissue factor, and chemokine release, with Human Microvascular Endothelial Cells (HMEC-1). ACE2 receptor expression was evaluated by western blot analysis. SARS-CoV-2 infection was assessed by one-step RT-PCR until 7 days post-infection (p.i.), and by Transmission Electron Microscopy (TEM). IL-6, TNF-α, IL-8, IFN-α, and hTF mRNA expression levels were detected by RT-PCR, while cytokine release was evaluated by ELISA. HMEC-1 expressed ACE2 receptor and SARS-CoV-2 infection showed a constant viral load. TEM analysis showed virions localized in the cytoplasm. Expression of IL-6 at 24 h and IFN-α mRNA at 24 h and 48 h p.i. was higher in infected than uninfected HMEC-1 (p < 0.05). IL-6 levels were significantly higher in supernatants from infected HMEC-1 (p < 0.001) at 24 h, 48 h, and 72 h p.i., while IL-8 levels were significantly lower at 24 h p.i. (p < 0.001). These data indicate that in vitro microvascular endothelial cells are susceptible to SARS-CoV-2 infection but slightly contribute to viral amplification. However, SARS-CoV-2 infection might trigger the increase of pro-inflammatory mediators.


Assuntos
COVID-19 , Enzima de Conversão de Angiotensina 2 , Quimiocinas/genética , Quimiocinas/metabolismo , Citocinas/metabolismo , Células Endoteliais/metabolismo , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , SARS-CoV-2
8.
J Med Food ; 25(4): 389-401, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35438553

RESUMO

Ulcerative colitis (UC) is a chronic idiopathic inflammatory disorder of the large intestine. Fructus mume (FM), a natural food with nutritive and pharmaceutical value, has demonstrated therapeutic efficacy against UC. In this study, we investigated the protective effects and mechanisms of FM against UC. We induced UC in rats with 4% (v/v) acetic acid (AA), orally administered 0.7 or 0.325 g/kg FM and 0.3 g/kg sulfasalazine (SASP) for 7 days, and explored the responses the drugs elicited in the rats. We assessed the general conditions of the rats by the disease active index. We evaluated colon tissue damage macroscopically and by Hematoxylin & Eosin, Alcian Blue-periodic acid-Schiff, and Masson's staining, and explored the potential mechanisms of FM on inflammation, oxidative stress, and neuropeptides by measuring TNF-α, IL-6, IL-8, IL-10, MMP9, CXCR-1, SOD, GSH-px, MDA, ROS, SIRT3, SP, VIP, ghrelin, and 5-HT. FM treatment significantly attenuated colon damage and submucosal fibrosis compared with the model. It lowered serum proinflammatory TNF-α, IL-8, and colonic MMP9 and CXCR-1, and raised serum anti-inflammatory IL-10 levels. FM upregulated the antioxidant enzymes SOD, GSH-px, and SITR3 protein but inhibited ROS and MDA production. It downregulated colonic SP, VIP, ghrelin, and 5-HT. The beneficial effects of FM might be dose dependent. Around 0.7 g/kg FM and SASP displayed similar efficacy for treating AA-induced colitis in rats. Our results provide empirical evidence that FM protects against AA-induced UC in rats via anti-inflammatory and antioxidant mechanisms, and regulates neuropeptides; thus, FM may be a promising, safe, and efficacious alternative therapy for UC, if its efficacy can be confirmed in human trials.


Assuntos
Colite Ulcerativa , Neuropeptídeos , Ácido Acético/efeitos adversos , Ácido Acético/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colo , Citocinas/metabolismo , Grelina/metabolismo , Interleucina-10/metabolismo , Interleucina-8/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Neuropeptídeos/metabolismo , Neuropeptídeos/farmacologia , Neuropeptídeos/uso terapêutico , Ratos , Espécies Reativas de Oxigênio/metabolismo , Serotonina/metabolismo , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
9.
Cell Death Dis ; 13(4): 294, 2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35365616

RESUMO

Adenosine (A) to inosine (I) RNA editing catalyzed by adenosine deaminases acting on RNA (ADAR) enzymes is a post-transcriptional modification that emerged as a key player in tumorigenesis and cancer progression. Antizyme inhibitor 1 (AZIN1) is one of the most frequent A-to-I RNA alterations in many human cancers. RNA-edited AZIN1 is known to confer a gain-of-function phenotype associated with aggressive tumors. However, the functional impact of RNA-edited AZIN1 in cancer angiogenesis remains unexplored. We showed here that RNA-edited AZIN1 promoted tumor angiogenesis through the upregulation of IL-8 via in vitro and in vivo experiments. And we subsequently demonstrated that delaying c-Myc degradation by OAZ2-mediated ubiquitin-independent proteasome pathway contributed to increase mRNA level and the secretion of angiogenic factor IL-8. Our study suggests an important contribution of RNA-edited AZIN1 to the tumor vascular microenvironment and highlights its translational potential. Thus, we revealed a potential approach to explore small-molecule antagonists such as reparixin attenuating IL-8 signaling for treatment of human cancer patients detected with hyper-editing.


Assuntos
Neoplasias Colorretais , Interleucina-8 , Adenosina , Adenosina Desaminase/metabolismo , Proteínas de Transporte/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Interleucina-8/genética , Interleucina-8/metabolismo , RNA , Microambiente Tumoral
10.
BMC Mol Cell Biol ; 23(1): 18, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35413833

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is the most severe type of breast cancer owing to its high heterogeneity, aggressiveness and lack of treatment. Studies have reported that uncarboxylated osteocalcin (GluOC) promotes the development of prostate and other cancers. Studies have also found elevated levels of serum osteocalcin in breast cancer patients with bone metastasis, and serum osteocalcin can be a marker of bone metastasis. However, whether GluOC promotes the development of TNBC and the related mechanisms need to be further clarified. RESULTS: Our results revealed that GluOC is associated with the proliferation and metastasis of MDA-MB-231 cells. GluOC increased the viability and proliferation of MDA-MB-231 cells. In addition, GluOC enhanced the metastatic ability of MDA-MB-231 cells by promoting the expression of matrix metalloproteinase-2 (MMP2), matrix metalloproteinase-13 (MMP13), and vascular endothelial growth factor (VEGF) and inducing epithelial-mesenchymal transition (EMT). We also found that GluOC upregulated the expression of interleukin-8 (IL-8) and parathyroid hormone-related protein (PTHrP) genes in MDA-MB-231 breast cancer cells. Moreover, the promoting effect of GluOC was reversed in MDA-MB-231 breast cancer cells treated with specific inhibitor of SMAD3 (SIS3), a SMAD3 phosphorylation inhibitor. CONCLUSION: Our research proved for the first time that GluOC facilitates the proliferation and metastasis of MDA-MB-231 cells by accelerating the transforming growth factor-ß (TGF-ß)/SMAD3 signaling pathway. Moreover, GluOC also promotes the gene expression of IL-8 and PTHrP. Both IL-8 and PTHrP can act as osteolytic factors in breast cancer cells. This study indicates that GluOC may be a useful target for preventing TNBC bone metastasis.


Assuntos
Osteocalcina , Proteína Relacionada ao Hormônio Paratireóideo , Fator de Crescimento Transformador beta , Neoplasias de Mama Triplo Negativas , Proliferação de Células , Humanos , Interleucina-8/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Osteocalcina/metabolismo , Proteína Relacionada ao Hormônio Paratireóideo/metabolismo , Proteína Relacionada ao Hormônio Paratireóideo/farmacologia , Transdução de Sinais , Proteína Smad3/metabolismo , Proteína Smad3/farmacologia , Fator de Crescimento Transformador beta/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
11.
Molecules ; 27(7)2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35408512

RESUMO

Present studies have shown that Flos Chrysanthemi has anti-inflammatory and other effects and regulates intestinal function, while the chrysanthemum stem and leaf as non-medicinal parts of chrysanthemum have similar chemical components with chrysanthemum, but the activity and mechanisms are rarely elucidated. Therefore, this study used a DSS-induced zebrafish inflammatory bowel disease model to study the anti-inflammatory and antioxidant effects of chrysanthemum stem and leaf extracts. The results indicate that DSS induction leads to increased secretion of acidic mucin in the intestines of juvenile fish, enlargement of the intestinal lumen and the emergence of intestinal inflammation. Compared with the model group, each administration group differentially inhibited the expression of IL-1ß, IL-8 and MMP9 in DSS-induced zebrafish, while upregulating the activity of superoxide dismutase. The quantitative analysis results showed that the flavonoids (including Linarin, Diosmetin-7-glucoside, Tilianin, etc.) and phenolic acids (including Isochlorogenic acid C, Isochlorogenic acid A, 1,3-Dicaffeoylquinic acid, etc.) in the alcohol extract were closely related with both anti-inflammatory and antioxidant activity, while the polysaccharides were also shown a certain anti-inflammatory and antioxidant activity. In conclusion, this study suggests that the flavonoids, phenolic acids and polysaccharides from chrysanthemum stem and leaf extracts can improve inflammatory bowel disease of zebrafish by regulating the expressions of IL-1ß, IL-8 and MMP9.


Assuntos
Chrysanthemum , Medicamentos de Ervas Chinesas , Doenças Inflamatórias Intestinais , Animais , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Chrysanthemum/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/análise , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/tratamento farmacológico , Interleucina-8/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Peixe-Zebra/metabolismo
12.
Sci Rep ; 12(1): 6710, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35468976

RESUMO

We aim to assess the effects of different air pollutants on meibomian gland dysfunction (MGD). As a prospective multicenter study, 864 patients were recruited from four different regions (i.e., coal, oil, steel, and living). The oil region had a significantly lower temperature and higher O3 and SO2 concentrations than other regions. Notably, participants in oil region presented with more frequent and serious MGD signs and higher cytokine levels (median interleukin 6 [IL-6] in oil: 2.66, steel: 0.96, coal: 0.38, living: 0.56; IL-8 in oil: 117.52, steel: 46.94, coal: 26.89, living: 33; vascular endothelial growth factor [VEGF] in oil: 25.09, steel: 14.02, coal: 14.02, living: 28.47). The short-term fluctuations of cytokine levels were associated with the changes in gas levels (PM2.5 and IL-8: ß = 0.016 [0.004-0.029]; O3 and IL-6: ß = 0.576 [0.386-0.702]; O3 and IL-8: ß = 0.479 [0.369-0.890]; SO2 and VEGF: ß = 0.021 [0.001-0.047]). After long-term exposure, lid margin neovascularization (r = 0.402), meibomian gland (MG) expression (r = 0.377), MG secretion (r = 0.303), MG loss (r = 0.404), and tear meniscus height (r = - 0.345) were moderately correlated with air quality index (AQI). Individuals in oil region had more serious MGD signs and higher cytokine levels. MGD is susceptible to long-term exposure to high AQI.


Assuntos
Poluição do Ar , Doenças Palpebrais , Disfunção da Glândula Tarsal , Poluição do Ar/efeitos adversos , Carvão Mineral , Citocinas/metabolismo , Doenças Palpebrais/induzido quimicamente , Doenças Palpebrais/diagnóstico , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Estudos Prospectivos , Aço , Lágrimas/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
13.
Oxid Med Cell Longev ; 2022: 9366494, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35450405

RESUMO

Trehalose, a natural disaccharide, is synthesized by many organisms when cells are exposed to stressful stimuli. On the basis of its ability to modulate autophagy, trehalose has been considered an innovative drug for ameliorating many diseases, but its molecular mechanism is not well described. Previous findings demonstrated that trehalose plays a photoprotective role against ultraviolet (UV) B-induced damage through autophagy induction in keratinocytes. In this study, coimmunoprecipitation, label-free quantitative proteomic and parallel reaction monitoring, and western blot analysis demonstrated that trehalose promotes the interaction between tissue inhibitor of metalloproteinase (TIMP) 3 and Beclin1. Western blot and immunofluorescence staining analysis suggested that trehalose increases ATG9A localization in lysosomes and decreases its localization in the endoplasmic reticulum. Furthermore, in the presence or absence of UVB radiation, we evaluated the influence of TIMP3 and ATG9A small interfering RNA (siRNA) on the effect of trehalose on autophagy, cell death, migration, or interleukin-8 expression in keratinocytes, including HaCaT, A431, and human epidermal keratinocytes. The results revealed that in HaCaT cells, TIMP3 and ATG9A siRNA resulted in attenuation of trehalose-induced autophagy and inhibited cell death. In A431 cells, TIMP3 and ATG9A siRNA led to attenuation of trehalose-induced autophagy and cell death and inhibited migration. In human epidermal keratinocytes, trehalose-induced autophagy and inhibition of the interleukin-8 expression were blocked by ATG9A but not TIMP3 siRNA. In addition, the results of quantitative real-time PCR and immunohistochemistry analysis demonstrated the abnormal expression of TIMP3 and ATG9A in actinic keratosis and cutaneous squamous cell carcinoma skin tissues. These findings suggest the protective effects of trehalose in normal keratinocytes and its inhibitory effects on cancerous keratinocytes, possibly mediated by activation of autophagy and regulation of TIMP3 and ATG9A, providing the mechanistic basis for the potential use of trehalose in the prevention or treatment of UVB-induced skin diseases.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Cutâneas , Autofagia , Proteínas Relacionadas à Autofagia/metabolismo , Carcinoma de Células Escamosas/patologia , Humanos , Interleucina-8/metabolismo , Queratinócitos/metabolismo , Proteínas de Membrana/metabolismo , Proteômica , RNA Interferente Pequeno/metabolismo , Neoplasias Cutâneas/metabolismo , Inibidor Tecidual de Metaloproteinase-3/genética , Inibidor Tecidual de Metaloproteinase-3/metabolismo , Inibidor Tecidual de Metaloproteinase-3/farmacologia , Trealose/farmacologia , Raios Ultravioleta/efeitos adversos , Proteínas de Transporte Vesicular/metabolismo
14.
Front Immunol ; 13: 865386, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35444648

RESUMO

Objective: In a recent study, we found an elevated level of interleukin 8 (IL-8) in response to bacterial incubation in thrombin-sufficient human whole blood anticoagulated by the fibrin polymerization blocking peptide GPRP. Whether thrombin directly activated leukocytes or mediated the release via thrombin-dependent activation of platelets remains unresolved. Herein, we addressed the role of thrombin and platelets in IL-8 release. Methods: We separated platelets from whole blood using a combination of 0.7% (w/v) citrate and GPRP for attenuating the hemostatic response during the separation of platelets. Cytokine responses were compared in whole blood and platelet-depleted blood upon Escherichia coli incubation. Cytokine responses were also profiled with and without reconstitution of either platelets or the supernatant from activated platelets. Results: Platelets were not activated during the separation process but responded to stimuli upon re-calcification. Plasma levels of IL-1ß, IL-1Ra, IL-6, IL-8, IP-10, MIP-1α, and MIP-1ß were significantly reduced in platelet-depleted blood compared to whole blood, but recovered in the presence of platelets, or with the supernatant of activated platelets. The leukocyte fraction and platelets were each found to contribute to the elevation of IL-8 at around 5 ng/ml; however, if combined, the release of IL-8 increased to 26 ng/ml. This process was dependent on thrombin since the levels of IL-8 remained at 5 ng/ml in whole blood if thrombin was blocked. Intracellular staining revealed that monocytes were the main source for IL-8 expression. Conclusion: Our findings suggest that the release of IL-8 is mediated by the leukocytes, mainly monocytes, but potentiated via thrombin-dependent activation of platelets.


Assuntos
Interleucina-8 , Trombina , Plaquetas/metabolismo , Citocinas/metabolismo , Humanos , Interleucina-8/metabolismo , Leucócitos/metabolismo , Trombina/metabolismo , Trombina/farmacologia
15.
Phytomedicine ; 100: 154082, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35381565

RESUMO

BACKGROUND: Extracellular vesicles (EVs) contribute greatly to the formation of pre-metastatic niche and tumor metastasis. Our previous study has revealed that tumor-derived ITGBL1 (integrin beta- like 1)-rich EVs activate fibroblasts through the NF-κB signaling to promote colorectal cancer (CRC) metastasis. Targeting ITGBL1-loaded EVs may be a new and effective therapy for treating CRC metastasis. Simultaneously, our preliminary clinical trial has demonstrated that Jianpi Jiedu Recipe (JPJDR) was an ideal alternative traditional Chinese medicine for the prevention and treatment of CRC metastasis. However, the underlying mechanism of JPJDR in the prevention of CRC metastasis is not clear. In this study, we will investigate the regulatory effect of JPJDR on ITGBL1 levels in CRC-derived EVs, and to detect how JPJDR regulate ITGBL1-rich EVs mediated activation of fibroblasts to inhibit CRC metastasis. METHODS: EVs derived from CRC cells with/without JPJDR treatment were obtained by ultracentrifugation, following by characterization with electron microscopy, LM10 nanoparticle characterization system and western blot. The migration and growth of CRC cells were tested by transwell assay, wound healing assay and colony formation assay. The effect of JPJDR on the fibroblasts-activation associated inflammatory factors including IL-6, IL-8 and α-SMA was detected by real-time PCR. The levels of IL-6, IL-8 and α-SMA in the cell culture supernatant were detected by ELISA. The protein expressions of TNFAIP3, ITGBL1, p-NF-κB, IκBα and ß-actin were detected by western blot. Liver metastasis model in mice was established by injecting MC38 single cell suspension into the spleen of mice to observe the effect of JPJDR on CRC liver metastasis. Immunohistochemistry were applied to detect the expression of ITGBL1 and TNFAIP3 in the liver metastatic tissues. Tissue immunofluorescence detection was performed to observe the regulatory effect of JPJDR on the ITGBL1-NF-κB signaling pathway. Cancer-associated fibroblasts (CAFs) in the liver metastatic tissues were sorted and characterized by platelet-derived growth factor receptor ß (PDGFRß) with flow cytometry, following by the detection of inflammatory factors including IL-6, IL-8 and α-SMA using real-time PCR. RESULTS: JPJDR reduced the ITGBL1 levels in CRC cells-derived EVs. JPJDR inhibited the migration and growth of CRC cells via regulating ITGBL1-rich EVs mediated fibroblasts activity. Mechanically, JPJDR decreased fibroblasts activation by regulating ITGBL1-rich EVs mediated TNFAIP3-NF-κB signaling. Further in vivo experiments demonstrated that JPJDR reduced CRC liver metastasis by regulating ITGBL1-rich EVs secretion from CRC and blocked the fibroblasts activation by regulating ITGBL1-TNFAIP3- NF-κB signaling. CONCLUSION: Our research demonstrated that JPJDR preventd CRC liver metastasis via down-regulating CRC-derived ITGBL1-loaded EVs mediated activation of CAFs, providing the experimental evidence for the clinical application of JPJDR in the prevention and treatment of CRC metastasis. More importantly, our study confirmed the great benefits of therapeutic targeting the EVs-mediated metastasis and warranted future clinical validation.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias Colorretais , Vesículas Extracelulares , Neoplasias Hepáticas , Animais , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Medicamentos de Ervas Chinesas , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/patologia , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , NF-kappa B/metabolismo , Metástase Neoplásica
16.
Nutrients ; 14(5)2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35268019

RESUMO

Helicobacter pylori (H. pylori) causes gastric diseases by increasing reactive oxygen species (ROS) and interleukin (IL)-8 expression in gastric epithelial cells. ROS and inflammatory responses are regulated by the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) and the expression of Nrf2 target genes, superoxide dismutase (SOD) and heme oxygenase-1 (HO-1). We previously demonstrated that Korean red ginseng extract (RGE) decreases H. pylori-induced increases in ROS and monocyte chemoattractant protein 1 in gastric epithelial cells. We determined whether RGE suppresses the expression of IL-8 via Nrf2 activation and the expression of SOD and HO-1 in H. pylori-infected gastric epithelial AGS cells. H. pylori-infected cells were treated with RGE with or without ML385, an Nrf2 inhibitor, or zinc protoporphyrin (ZnPP), a HO-1 inhibitor. Levels of ROS and IL-8 expression; abundance of Keap1, HO-1, and SOD; levels of total, nuclear, and phosphorylated Nrf2; indices of mitochondrial dysfunction (reduction in mitochondrial membrane potential and ATP level); and SOD activity were determined. As a result, RGE disturbed Nrf2-Keap1 interactions and increased nuclear Nrf2 levels in uninfected cells. H. pylori infection decreased the protein levels of SOD-1 and HO-1, as well as SOD activity, which was reversed by RGE treatment. RGE reduced H. pylori-induced increases in ROS and IL-8 levels as well as mitochondrial dysfunction. ML385 or ZnPP reversed the inhibitory effect of RGE on the alterations caused by H. pylori. In conclusion, RGE suppressed IL-8 expression and mitochondrial dysfunction via Nrf2 activation, induction of SOD-1 and HO-1, and reduction of ROS in H. pylori-infected cells.


Assuntos
Mucosa Gástrica , Infecções por Helicobacter , Interleucina-8 , Fator 2 Relacionado a NF-E2 , Panax , Extratos Vegetais , Linhagem Celular Tumoral , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Células Epiteliais/virologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Mucosa Gástrica/virologia , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/patologia , Infecções por Helicobacter/virologia , Helicobacter pylori , Humanos , Interleucina-8/biossíntese , Interleucina-8/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Mitocôndrias/química , Mitocôndrias/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Panax/metabolismo , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo
17.
Circ Res ; 130(7): 1014-1029, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35264012

RESUMO

BACKGROUND: Ischemic heart disease following the obstruction of coronary vessels leads to the death of cardiac tissue and the formation of a fibrotic scar. In contrast to adult mammals, zebrafish can regenerate their heart after injury, enabling the study of the underlying mechanisms. One of the earliest responses following cardiac injury in adult zebrafish is coronary revascularization. Defects in this process lead to impaired cardiomyocyte repopulation and scarring. Hence, identifying and investigating factors that promote coronary revascularization holds great therapeutic potential. METHODS: We used wholemount imaging, immunohistochemistry and histology to assess various aspects of zebrafish cardiac regeneration. Deep transcriptomic analysis allowed us to identify targets and potential effectors of Vegfc (vascular endothelial growth factor C) signaling. We used newly generated loss- and gain-of-function genetic tools to investigate the role of Emilin2a (elastin microfibril interfacer 2a) and Cxcl8a (chemokine (C-X-C) motif ligand 8a)-Cxcr1 (chemokine (C-X-C) motif receptor 1) signaling in cardiac regeneration. RESULTS: We first show that regenerating coronary endothelial cells upregulate vegfc upon cardiac injury in adult zebrafish and that Vegfc signaling is required for their proliferation during regeneration. Notably, blocking Vegfc signaling also significantly reduces cardiomyocyte dedifferentiation and proliferation. Using transcriptomic analyses, we identified emilin2a as a target of Vegfc signaling and found that manipulation of emilin2a expression can modulate coronary revascularization as well as cardiomyocyte proliferation. Mechanistically, Emilin2a induces the expression of the chemokine gene cxcl8a in epicardium-derived cells, while cxcr1, the Cxcl8a receptor gene, is expressed in coronary endothelial cells. We further show that Cxcl8a-Cxcr1 signaling is also required for coronary endothelial cell proliferation during cardiac regeneration. CONCLUSIONS: These data show that after cardiac injury, coronary endothelial cells upregulate vegfc to promote coronary network reestablishment and cardiac regeneration. Mechanistically, Vegfc signaling upregulates epicardial emilin2a and cxcl8a expression to promote cardiac regeneration. These studies aid in understanding the mechanisms underlying coronary revascularization in zebrafish, with potential therapeutic implications to enhance revascularization and regeneration in injured human hearts.


Assuntos
Interleucina-8 , Glicoproteínas de Membrana , Fator C de Crescimento do Endotélio Vascular , Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Proliferação de Células , Células Endoteliais/metabolismo , Coração/fisiologia , Interleucina-8/metabolismo , Mamíferos , Glicoproteínas de Membrana/metabolismo , Miócitos Cardíacos/metabolismo , Regeneração/fisiologia , Fator C de Crescimento do Endotélio Vascular/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
18.
Cytokine ; 153: 155828, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35247648

RESUMO

Early in the 1980s several laboratories mistakenly reported that partially purified interleukin-1 (IL-1) was chemotactic for neutrophils. However, further investigations by us, revealed that our purified IL-1 did not have neutrophil chemotactic activity and this activity in the LPS-stimulated human monocyte conditioned media could clearly be separated from IL-1 activity on HPLC gel filtration. This motivated Teizo Yoshimura and Kouji Matsushima to purify the monocyte-derived neutrophil chemotactic factor (MDNCF), present in LPS conditioned media and molecularly clone the cDNA for MDNCF. They found that MDNCF protein (later renamed IL-8, and finally termed CXCL8) is first translated as a precursor form consisting of 99 amino acid residues and the signal peptide is then removed, leading to the secretion and processing of biologically active IL-8 of 72 amino acid form (residues 28-99). There are four cysteine residues forming two disulfide linkage and 14 basic amino acid residues which result in a very basic property for the binding of IL-8 to heparan sulfate-proteoglycan. The IL-8 gene consists of 4 exons and 3 introns. IL-8 is produced by various types of cells in inflammation. The 5'-flanking region of IL-8 gene contains several nuclear factor binding sites, and NF-κB in combination with AP-1 or C/EBP synergistically activates IL-8 gene in response to IL-1 and TNFα. Two receptors exist for IL-8, CXCR1 and CXCR2 in humans, which belong to γ subfamily of GTP binding protein (G-protein) coupled rhodopsin-like 7 transmembrane domain receptors. Rodents express CXCR2 and do not produce IL-8, but produce numerous homologues instead. Once IL-8 binds to the receptor, ß and γ subunits of G-protein are released from Gα (Gαi2 in neutrophils) and activate PI3Kγ, PLCß2/ß3, PLA2 and PLD. Gαi2 inhibits adenyl cyclase to decrease cAMP levels. Small GTPases Ras/Rac/Rho/cdc42/Rap1, PKC and AKT (PKB) exist down-stream of ß and γ subunits and regulate cell adhesion, actin polymerization, membrane protrusion, and eventually cell migration. PLCß activation generates IP3 and induces Ca++ mobilization, DAG generation to activate protein kinase C to lead granule exocytosis and respiratory burst. MDNCF was renamed interleukin 8 (IL-8) at the International Symposium on Novel Neutrophil Chemotactic Activating Polypeptides, London, UK in 1989. The discovery of IL-8 prompted us to also purify and molecularly clone the cDNA of MCAF/MCP-1 responsible for monocyte chemotaxis, and other groups to identify a large family of chemotactic cytokines capable of attracting other types of leukocytes. In 1992, most of the investigators contributing to the discovery of this new family of chemotactic cytokines gathered in Baden, Austria and agreed to name this family "chemokines" and subsequently established the CXCL/CCL and CXCR/CCR nomenclature. The discovery of chemokines resulted in solving the long-time enigma concerning the mechanism of cell type specific leukocyte infiltration into inflamed tissues and provided a molecular basis for immune and hematopoietic cell migration and interactions under physiological as well as pathological conditions. To our surprise based on its recently identified multifunctional activities, IL-8 has evolved from a neutrophil chemoattractant to a promising therapeutic target for a wide range of inflammatory and neoplastic diseases. IL-8 was initially characterized as a chemoattractant of neutrophils engaged in acute inflammation and then discovered to also be chemotactic for endothelial cells with a major role in angiogenesis. These two activities of IL-8 foster its stimulatory effect on tumor growth. This is abetted by recent additional discoveries showing that IL-8 has stimulatory effects on stem cells and can therefore directly promote the growth of receptor expressing cancer stem cells. IL-8 by interacting with bone marrow stem/progenitor cells has also the capacity to mobilize and release hematopoietic cells into the peripheral circulation. This includes the mobilization of neutrophilic myeloid-derived suppressor cells (N-MDSC) to infiltrate into tumors and thus further promotes the immune escape of tumors. Finally, the capacity of IL-8 to induce trans-differentiation of epithelial cancer cells into mesenchymal phenotype (EMT) increases the malignancy of tumors by promoting their metastatic spread and resistance to chemotherapeutics and cytotoxic immune cells. These observations have stimulated considerable current efforts to develop receptor antagonists for IL-8 and humanized anti-IL-8 antibody for the therapy of cancer, particularly in combination with immune checkpoint inhibitors, such as anti-PD-1/PD-L1 antibodies.


Assuntos
Interleucina-8 , Lipopolissacarídeos , Aminoácidos/metabolismo , Quimiocina CCL2/metabolismo , Quimiocinas/metabolismo , Meios de Cultivo Condicionados/metabolismo , DNA Complementar , Células Endoteliais , Humanos , Inflamação/metabolismo , Interleucina-1/metabolismo , Interleucina-8/metabolismo , Lipopolissacarídeos/farmacologia , Neutrófilos/metabolismo , Receptores de Interleucina-8B/genética , Receptores de Interleucina-8B/metabolismo
19.
Int J Mol Sci ; 23(6)2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35328451

RESUMO

BACKGROUND: Asian sand dust (ASD) and Aspergillus fumigatus are known risk factors for airway mucosal inflammatory diseases. Bacterial and fungal biofilms commonly coexist in chronic rhinosinusitis and fungus balls. We evaluated the effects of ASD on the development of A. fumigatus biofilm formation on nasal epithelial cells. METHODS: Primary nasal epithelial cells were cultured with A. fumigatus conidia with or without ASD for 72 h. The production of interleukin (IL)-6, IL-8, and transforming growth factor (TGF)-ß1 from nasal epithelial cells was determined by the enzyme-linked immunosorbent assay. The effects of ASD on A. fumigatus biofilm formation were determined using crystal violet, concanavalin A, safranin staining, and confocal scanning laser microscopy. RESULTS: ASD and A. fumigatus significantly enhanced the production of IL-6 and IL-8 from nasal epithelial cells. By coculturing A. fumigatus with ASD, the dry weight and safranin staining of the fungal biofilms significantly increased in a time-dependent manner. However, the increased level of crystal violet and concanavalin A stain decreased after 72 h of incubation. CONCLUSIONS: ASD and A. fumigatus induced the production of inflammatory chemical mediators from nasal epithelial cells. The exposure of A. fumigatus to ASD enhanced the formation of biofilms. The coexistence of ASD and A. fumigatus may increase the development of fungal biofilms and fungal inflammatory diseases in the sinonasal mucosa.


Assuntos
Aspergillus fumigatus , Areia , Aspergillus fumigatus/metabolismo , Biofilmes , Concanavalina A/farmacologia , Poeira , Células Epiteliais/metabolismo , Violeta Genciana/metabolismo , Violeta Genciana/farmacologia , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Mucosa Nasal/metabolismo
20.
Int J Mol Sci ; 23(5)2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35269618

RESUMO

There is a lack of in vitro models able to plausibly represent the inflammation microenvironment of knee osteoarthritis (OA). We analyzed the molecules released from OA tissues (synovial membrane, cartilage, infrapatellar fat pad) and investigated whether the stimulation of human synovial fibroblasts (SFs), with synthetic cytokines (IL-1ß and TNF-α or IFN-γ) or conditioned media (CM) from OA tissues, influence the SFs' response, in the sense of pro-inflammatory cytokines, chemokines, growth factors, and degradative enzymes modulation. Human SFs were obtained from OA synovial membranes. SFs and their CM were analyzed for biomarkers, proliferation rate, protein profile and gene expression, before and after stimulation. Real-time PCR and multiplex assays quantified OA-related gene expression and biomolecule production. Unlike other activators, CM from OA synovial membrane (CM-SM), significantly up-regulated all genes of interest (IL-6, IL-8, MMP-1, MMP-3, RANTES, MCP-1, TSG-6, YKL-40) in SFs. Multiplex immunoassay analysis showed that levels of OA-related cytokines (IL-6, IL-8, MCP 1, IL-1Ra), chemokine (RANTES) and growth factor (VEGF), produced by CM-SM stimulated SFs, increased significantly compared to non-stimulated SFs. Molecules released from the SM from OA patients induces OA-like changes in vitro, in specific OA synovial populations (SFs). These findings promote the use and establish a compelling in vitro model that simulates the versatility and complexity of the OA disease. This model, in the future, will allow us to study new cell therapies or test drugs by reducing or avoiding animal models.


Assuntos
Quimiocina CCL5 , Osteoartrite do Joelho , Animais , Quimiocina CCL5/metabolismo , Quimiocinas/metabolismo , Meios de Cultivo Condicionados/metabolismo , Citocinas/metabolismo , Fibroblastos/metabolismo , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Osteoartrite do Joelho/metabolismo , Membrana Sinovial/metabolismo
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