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1.
J Ethnopharmacol ; 301: 115758, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36167232

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional medicine, seeds of Ginkgo biloba L. (Gbs) have been used to treat cough or asthma for a long time. It is commonly used in clinic for lung diseases. However, its mechanism of lung protection is not completely clear. AIMS OF THE STUDY: This research was designed to explore the protective effects of Gbs on antioxidant and inflammation during the chronic obstructive pulmonary disease (COPD) pathological process provoked by cigarette smoking (CS) in rats. MATERIALS AND METHODS: Six random groups including control group, CS model group, Gbs intervention groups (25 mg/kg, 50 mg/kg, and 100 mg/kg) and aminophylline group were composed of forty-eight rats. Smoking and intratracheal instillation of lipopolysaccharide (LPS) were used to establish the COPD rat model. Glutathione peroxidase (GSH-PX), malondialdehyde (MDA), superoxide dismutase (SOD), and enzyme-linked immunosorbent assay (ELISA) was used for quantifying the inflammatory factors such as IL-8, IL-6, IL-10, IL-17 and TNF-α. Western blotting were used for detecting the protein expressions of Nrf2, Keap1 and HO-1 in the lung tissues. RESULTS: Gbs inhibits lung histological changes and decreased the inflammatory factors in both bronchoalveolar lavage fluid (BALF) and serum of CS-exposed rats, including IL-10, IL-17, IL-6, IL-8 and TNF-α. Gbs also inhibited the MDA level, increased SOD and GSH-PX activity in serum and changed expressions of Nrf2, Keap1 and HO-1 in the lung tissues. CONCLUSION: Gbs inhibit oxidative stress and inflammation induced by cigarette smoke in COPD rats through the Nrf2 Pathway.


Assuntos
Fumar Cigarros , Doença Pulmonar Obstrutiva Crônica , Animais , Ratos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Fumar Cigarros/efeitos adversos , Ginkgo biloba , Inflamação/patologia , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Pulmão , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Sementes/metabolismo , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
2.
J Ethnopharmacol ; 301: 115837, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36252875

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: During the Eastern Han Dynasty, Zhang Zhongjing first recorded the Gancao Fuzi decoction (GCFZD) formula in the "Synopsis of the Golden Chamber", which is reportedly an effective and safe treatment for rheumatoid arthritis (RA). However, the mechanism underlying the observed improvement in the T helper 17 (Th17)/regulatory T (Treg) cell imbalance in RA obtained with GCFZD has not been reported. AIM OF THE STUDY: This study aimed to demonstrate whether GCFZD ameliorated RA by modulating the Th17/Treg imbalance in RA mice. MATERIALS AND METHODS: Collagen was used to induce a model of collagen-induced arthritis (CIA) in mice. GCFZD was administered by gavage, and the arthritis index score, imaging and histopathological changes of the ankle joints, and the levels of the immunoglobulin G (IgG) class antibodies and proinflammatory factors in serum were determined. In addition, the frequencies of Th17 and Treg cells, the levels of relevant transcription factors and functional factors and the miR-34a gene in the spleen and the levels of interleukin-17A (IL-17A) and IL-10 in serum were determined. RESULTS: GCFZD significantly reduced the arthritis score, improved joint swelling and bone damage, reduced the pathological score, and decreased the serum levels of IgG class antibody (IgG and IgG2a) and proinflammatory factor [tumour necrosis factor-alpha (TNF-α), IL-1ß and IL-6]. Moreover, the Th17-cell proportion, the expression level of the Th17-specific transcription factor retinoic acid-related orphan receptor γt (RORγt) and functional factor IL-17A in the spleen, and the serum IL-17A level were decreased, whereas the Treg cell proportion, expression levels of the Treg-specific transcription factor forkhead box P3 (Foxp3) and functional factor IL-10 in the spleen, and the serum IL-10 level were increased. Furthermore, GCFZD inhibited miR-34a gene expression while promoting Foxp3 protein expression. CONCLUSIONS: The findings of this study demonstrate the therapeutic effect of GCFZD on mice with CIA, and the mechanism is related to an improvement in the Th17/Treg cell imbalance by targeting Foxp3 via miR-34a.


Assuntos
Artrite Experimental , Artrite Reumatoide , MicroRNAs , Camundongos , Animais , Linfócitos T Reguladores , Interleucina-17/metabolismo , Interleucina-10/metabolismo , Células Th17 , Artrite Reumatoide/patologia , Artrite Experimental/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Imunoglobulina G , Fatores de Transcrição/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo
3.
J Ethnopharmacol ; 300: 115741, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36162543

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Pulsatilla decoction (PD), is an herbal formula commonly used for the treatment of ulcerative colitis (UC) in clinical practice, but the mechanism of PD alters the colitis remains elusive. AIM OF THE STUDY: To evaluate the intervention effect of PD on Dextran Sodium Sulfate (DSS)-induced UC based on gut microbiota and intestinal short-chain fatty acid (SCFAs) metabolism, and to investigate the mechanism of action of PD in treating UC. MATERIALS AND METHODS: A 3% (wt/vol) DSS-induced ulcerative colitis model in C57BL/6 male mice was used to evaluate the effect of oral PD in treating UC. The changes in gut microbiota in mice were analyzed by 16SrDNA gene sequencing, and the content of SCFAs in the intestinal contents of mice was determined by gas chromatography-mass spectrometry (GC-MS). Enzyme-linked immunosorbent assay (ELISA) was applied to analyze the expression of inflammatory cytokines in serum and colonic tissues, and western blotting (WB) was applied to analyze the expression of tight junction proteins in colonic tissues. RESULTS: PD can alleviate the symptoms of UC mice, Pulsatilla Decoction high dose treatment group (PDHT) shows the best effect. Compared with the DSS group, the PDHT had significantly lower body mass, disease activity index (DAI) score, colonic macroscopic damage index (CMDI) score, and pathological damage score, at the phylum level, the relative abundance of Bacteroidetes increased while that of Firmicutes and Proteobacteria decreased, at the Genus level, the abundance of Bacteroides and Lachnospiraceae.NK4A136.group increased while that of Clostridium. sensu.stricto。, Escherichia. shigella and Turicibacter decreased. Compared with the DSS group, acetate, propionate, and total SCFAs in the PDHT with significantly higher levels. The concentrations of interleukin-1ß (L-1ß), tumor necrosis factor-alpha (TNF-α), and interleukin-17 (IL-17) decreased whereby the concentration of interleukin-10 (IL-10) increased in the PDHT group. The expression levels of Occludin, zonula occludens-1 (ZO-1), Claudin1, Claudin5, G protein-coupled receptor43 (GPR43) protein, and the relative expression of ZO-1 and Occludin mRNA were significantly increased PDHT group. CONCLUSIONS: PD has a good therapeutic effect on UC mice. The pharmacological mechanism is probably maintaining the homeostasis and diversity of gut microbiota, increasing the content of SCFAs, and repairing the colonic mucosal barrier.


Assuntos
Colite Ulcerativa , Colite , Pulsatilla , Animais , Bactérias/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo , Citocinas/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Ácidos Graxos Voláteis/metabolismo , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Interleucina-1beta/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ocludina/metabolismo , Propionatos , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
4.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(5): 777-784, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36325774

RESUMO

Objective To explore the effect and mechanism of hesperidin in treating the lung injury in the mouse model of respiratory syncytial virus (RSV)-induced bronchiolitis. Methods A mouse model of RSV-induced bronchiolitis was established,and 60 BALB/c mice were assigned into a control group,a model group,a low-dose hesperidin (18 mg/kg) group,a high-dose hesperidin (36 mg/kg) group,and a high-dose hesperidin (36 mg/kg)+Jagged1(1 mg/kg) group by random number table method,with 12 mice in each group. Corresponding doses of drugs were administrated for intervention,and the control group and model group were administrated with the same amount of saline.The bronchoalveolar lavage fluid (BALF) samples were collected and alveolar macrophages were isolated.ELISA was employed to detect the levels of interleukin (IL)-4,IL-6,tumor necrosis factor-α (TNF-α),and IL-10 in BALF,and flow cytometry to detect the M1/M2 polarization of macrophages.qRT-PCR and Western blotting were respectively conducted to detect the mRNA and protein levels of inducible nitric oxide synthase (iNOS),arginase 1 (Arg-1),Jagged1,and Notch1 in the lung tissue. Results Compared with the control group,the modeling of RSV-induced bronchiolitis elevated the IL-4,IL-6,and TNF-α levels,increased the proportion of M1-type macrophages and the lung inflammation and mucus secretion scores,and up-regulated the mRNA and protein levels of iNOS,Jagged1,and Notch1 in BALF (all P<0.001).Meanwhile,the modeling lowered the IL-10 level,decreased the proportion of M2-type macrophages,and down-regulated the mRNA and protein levels of Arg-1 (all P<0.001).Compared with the model group,low- and high-dose hesperidin lowered the IL-4,IL-6,TNF-α levels,decreased the proportion of M1-type macrophages and the lung inflammation and mucus secretion scores,and down-regulated the mRNA and protein levels of iNOS,Jagged1,and Notch1 in BALF (all P<0.05).Moreover,hesperidin elevated the IL-10 level,increased the proportion of M2-type macrophages,and up-regulated the mRNA and protein levels of Arg-1 (all P<0.001).Using recombinant Jagged1 protein to activate Notch1 signaling pathway can significantly attenuate the promotion of high-dose hesperidin on M2 macrophage polarization and amelioration of lung inflammation damage (all P<0.01). Conclusion Hesperidin may alleviate the lung inflammation damage in mice with RSV-induced bronchiolitis by inhibiting the Jagged1/Notch1 signaling pathway and promoting the M2-type polarization of macrophages.


Assuntos
Bronquiolite , Hesperidina , Lesão Pulmonar , Animais , Camundongos , Bronquiolite/metabolismo , Hesperidina/farmacologia , Hesperidina/uso terapêutico , Hesperidina/metabolismo , Interleucina-10/metabolismo , Interleucina-10/farmacologia , Interleucina-4/metabolismo , Interleucina-4/farmacologia , Interleucina-6/metabolismo , Proteína Jagged-1/metabolismo , Proteína Jagged-1/farmacologia , Lesão Pulmonar/metabolismo , Macrófagos , Camundongos Endogâmicos BALB C , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
5.
Int J Med Mushrooms ; 24(11): 1-20, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36374945

RESUMO

Mushrooms have become an important way to safely supply the body with the daily needs of organic selenium and they also possess remarkable medicinal properties. In this study, we examined the ability of the Pleurotus ostreatus mushroom to grow in selenium (Se) and its ability to accumulate and convert Se from inorganic form to organic form during growth. Additionally, we achieved the potential anticancer properties of mushroom extract in colon cancer cells using the CaCo-2 cell and the normal human colon mucosal epithelial cell line, NCM-460 cell line. Interestingly, Se-enriched mushroom extract (SME) showed a competitive regulation in colon cancer cell line; CaCo-2 cell line indicated by cell morphology, the number of survived cells, lactate dehydrogenase (LDH) production, and cell viability rate. Moreover, SME treatment regulates the expression profile of the cancer cell proliferation factor Raf-1 and pro-apoptotic related factors P53 and Caspase-3 Furthermore, the production of inflammatory-regulated cytokines, including interleukin 6 (IL-6) and IL-10, increased. At the same time, the level of produced tumor necrosis factor-alpha (TNF-α) markedly decreased in a dose and time-dependent of colon cancer-treated cells. Notably, the purified selenomethionine (SeMe) showed sufficient inhibition of colon cancer proliferation compared with the inorganic form of selenium (sodium selenite) via blocking the Raf/MEK/ERK signaling pathway. In addition, SeMe treatment also stimulated the production of IL-6 and IL-10 while decreasing the production of TNF-α, which plays a crucial role in the necrotic event. Meanwhile, the SeMe treatment showed a neglected cytotoxic effect in the normal colon epithelial cells. Collectively, these findings indicate that the fruiting bodies of Se-enriched mushrooms revealed anti-colon cancer activity via targeting Raf-1 signaling pathway and increasing the production of IL-6 and IL-10.


Assuntos
Neoplasias do Colo , Pleurotus , Selênio , Animais , Humanos , Antioxidantes/metabolismo , Células CACO-2 , Neoplasias do Colo/tratamento farmacológico , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Pleurotus/química , Selênio/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
6.
J Tradit Chin Med ; 42(6): 956-964, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36378054

RESUMO

OBJECTIVE: To evaluate the effect of compound Gaoziban tablet (, CGZBT) on depression, and to investigate the underlying mechanism. METHODS: The components of CGZBT were analysed by high-performance liquid chromatography. Then, we assessed the effects of varying doses of CGZBT on an established chronic unpredictable mild stress (CUMS) model in rats. Whether animals were depressed was evaluated by sucrose preference test, open field test and forced swimming test. Neurotransmitters of hippocampus were detected by liquid chromatography-mass spec-trometry. Serum levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, IL-6, IL-4, and IL-10 were measured by enzyme-linked immunosorbent assay. Expressions of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), phospho-nuclear factor-kappa B (p-NF-κB), cyclooxygenase-2 (COX-2), ionized calcium binding adapter molecule-1 (IBA-1) were assessed by immunohistochemical staining and western blotting. RESULTS: Eight compounds were identified from CGZBT, moreover, our results showed that CGZBT effectively reversed the CUMS-induced decrease in sucrose preference, shortened the movement distance and prolonged immobility time. CGZBT significantly increased levels of 5-hydroxytryptamine, dopamine, norepinephrine, 5-hydroxyindoleacetic acid levels, and reduced the expression of TNF-α, IL-1ß, IL-6, yet increased IL-4 and IL-10. Furthermore, the expressions of TLR4, MyD88, COX-2, p-NF-κB and IBA-1 in hippocampus were effectively reversed after treatment with CGZBT. CONCLUSIONS: These results indicated that CGZBT could, at least in part, alleviate depression induced by CUMS the TLR4/MyD88/NF-κB pathway, suggesting its potential as an antidepressant drug.


Assuntos
Fator 88 de Diferenciação Mieloide , NF-kappa B , Ratos , Animais , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Interleucina-10/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Depressão/tratamento farmacológico , Interleucina-6/metabolismo , Ciclo-Oxigenase 2/metabolismo , Interleucina-4 , Transdução de Sinais , Comprimidos/farmacologia , Sacarose/farmacologia
7.
Int J Mol Sci ; 23(21)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36361795

RESUMO

Neuropeptide Y (NPY) is an abundantly expressed peptide capable of modulating innate and adaptive immune responses and regulating chemotaxis and cytokine secretion by macrophages. Abnormal regulation of NPY is involved in the development of atherosclerosis. The inflammatory infiltrate within atherosclerotic plaque is characterized by accumulation of macrophages, which are subject to reprogram their phenotypes in response to environmental signals. Macrophage number and phenotype influence plaque fate. Here, we investigated the effect of NPY on the changes in phenotype and functions of human macrophages, from the pro-inflammatory phenotype M1 to the reparative M2, indicative of atherosclerosis regression or stabilization. Human monocytes were differentiated in vitro into macrophages with M-CSF (M0) and polarized towards an M1 phenotype with IFN-γ plus LPS M(IFN-γ/LPS) or M2 with IL-10 (M IL-10) and further challenged with NPY (10-7-10-9 M) for 8-36 h. Cell phenotype and functions were analyzed by immunofluorescence and immunochemical analyses. NPY affected macrophage surface markers and secretome profile expression, thus shifting macrophages toward an M2-like phenotype. NPY also prevented the impairment of endocytosis triggered by the oxysterol 7-keto-cholesterol (7KC) and prevented 7KC-induced foam cell formation by reducing the lipid droplet accumulation in M0 macrophages. NPY-treated M0 macrophages enhanced the autophagosome formation by upregulating the cell content of the autophagy markers LC3-II and p62-SQSTM1, increased activation of the anti-oxidative transcription factor NRF2 (NF-E2-related factor 2), and subsequently induced its target gene HMOX1 that encodes heme oxygenase-1. Our findings indicate that NPY has a cytoprotective effect with respect to the progression of the inflammatory pathway, both enhancing p62/SQSTM1-dependent autophagy and the NRF2-antioxidant signaling pathway in macrophages. NPY signaling may have a crucial role in tissue homeostasis in host inflammatory responses through the regulation of macrophage balance and functions within atherosclerosis.


Assuntos
Aterosclerose , Interleucina-10 , Humanos , Interleucina-10/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Neuropeptídeo Y/metabolismo , Proteína Sequestossoma-1/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Ativação de Macrófagos , Autofagia , Aterosclerose/metabolismo
8.
Cells ; 11(21)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36359814

RESUMO

Low back pain is a clinically highly relevant musculoskeletal burden and is associated with inflammatory as well as degenerative processes of the intervertebral disc. However, the pathophysiology and cellular pathways contributing to this devastating condition are still poorly understood. Based on previous evidence, we hypothesize that tissue renin-angiotensin system (tRAS) components, including the SARS-CoV-2 entry receptor angiotensin-converting enzyme 2 (ACE2), are present in human nucleus pulposus (NP) cells and associated with inflammatory and degenerative processes. Experiments were performed with NP cells from four human donors. The existence of angiotensin II, angiotensin II type 1 receptor (AGTR1), AGTR2, MAS-receptor (MasR), and ACE2 in human NP cells was validated with immunofluorescent staining and gene expression analysis. Hereafter, the cell viability was assessed after adding agonists and antagonists of the target receptors as well as angiotensin II in different concentrations for up to 48 h of exposure. A TNF-α-induced inflammatory in vitro model was employed to assess the impact of angiotensin II addition and the stimulation or inhibition of the tRAS receptors on inflammation, tissue remodeling, expression of tRAS markers, and the release of nitric oxide (NO) into the medium. Furthermore, protein levels of IL-6, IL-8, IL-10, and intracellular as well as secreted angiotensin II were assessed after exposing the cells to the substances, and inducible nitric oxide synthase (iNOS) levels were evaluated by utilizing Western blot. The existence of tRAS receptors and angiotensin II were validated in human NP cells. The addition of angiotensin II only showed a mild impact on gene expression markers. However, there was a significant increase in NO secreted by the cells. The gene expression ratios of pro-inflammatory/anti-inflammatory cytokines IL-6/IL-10, IL-8/IL-10, and TNF-α/IL-10 were positively correlated with the AGTR1/AGTR2 and AGTR1/MAS1 ratios, respectively. The stimulation of the AGTR2 MAS-receptor and the inhibition of the AGTR1 receptor revealed beneficial effects on the gene expression of inflammatory and tissue remodeling markers. This finding was also present at the protein level. The current data showed that tRAS components are expressed in human NP cells and are associated with inflammatory and degenerative processes. Further characterization of the associated pathways is warranted. The findings indicate that tRAS modulation might be a novel therapeutic approach to intervertebral disc disease.


Assuntos
Núcleo Pulposo , Sistema Renina-Angiotensina , Humanos , Angiotensina II/metabolismo , Enzima de Conversão de Angiotensina 2 , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Núcleo Pulposo/citologia , Núcleo Pulposo/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
9.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(5): 785-793, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36325775

RESUMO

Objective To explore the role and mechanism of microRNA-204(miR-204) carried by the exosomes of human umbilical cord-derived mesenchymal stem cells(hUC-MSC) in regulating the polarization of macrophages in a mouse model of myocardial ischemia-reperfusion(I/R) injury. Methods After the hUC-MSCs were isolated,cultured,and identified,their adipogenic and osteogenic differentiation capabilities were determined.The exosomes of hUC-MSCs were separated by ultracentrifugation,and the expression of CD81,CD63,tumor susceptibility gene 101(Tsg101),and calnexin in the exosomes was determined by Nanoparticle Tracking Analysis software,transmission electron microscopy,and Western blotting.Three groups(hUC-MSC,miR-204 mimic,and negative control) were designed for the determination of the expression of miR-204 in the cells and their exosomes by qRT-PCR.The C57BL/6J mice were randomly assigned into a sham operation group,an I/R group,a hUC-MSC exosomes group,a negative control group,and a miR-204 mimic group.Except the sham operation group,the I/R model was established by ligating the left anterior descending artery.The echocardiography system was employed to detect the heart function of mice.HE staining was employed to observe the pathological changes of mouse myocardium.ELISA was employed to determine the levels of interleukin-1ß(IL-1ß),tumor necrosis factor-α(TNF-α),arginase 1(Arg-1),and IL-10 in the myocardial tissue.After the macrophages of mouse myocardial tissue were isolated,flow cytometry was employed to determine the expression of CD11c and CD206,and ELISA to measure the levels of IL-1ß,TNF-α,Arg-1,and IL-10 in the macrophages. Results hUC-MSCs had adipogenic and osteogenic differentiation capabilities,and the exosomes were successfully identified.Compared with the negative control group,the miR-204 mimic group showed up-regulated expression of miR-204 in hUC-MSCs and their exosomes(P<0.001,P<0.001).Compared with the sham operation group,the modeling of I/R increased the left ventricular end-diastolic diameter(LVEDD)(P<0.001),left ventricular end-systolic diameter(LVESD)(P<0.001),myocardial injury score(P<0.001),and the levels of IL-1ß(P<0.001),TNF-α(P<0.001),and CD11c(P<0.001).Meanwhile,it lowered the left ventricular ejection fraction(LVEF)(P<0.001),left ventricular fractional shortening(LVFS)(P<0.001),Arg-1(P<0.001),IL-10(P<0.001),and CD206(P<0.001).Compared with those in the I/R group,the LVEDD(P<0.001),LVESD(P<0.001),myocardial injury score(P<0.001),and the levels of IL-1ß(P<0.001),TNF-α(P=0.010),and CD11c(P<0.001) reduced,while LVEF(P<0.001),LVFS(P<0.001),and the levels of Arg-1(P<0.001),IL-10(P=0.028),and CD206(P=0.022) increased in the hUC-MSC exosomes group.Compared with those in the negative control group,the LVEDD(P<0.001),LVESD(P<0.001),myocardial injury score(P=0.001),and the levels of IL-1ß(P=0.048),TNF-α(P<0.001),and CD11c(P=0.007) reduced,while the LVEF(P<0.001),LVFS(P<0.001),and the levels of Arg-1(P<0.001),IL-10(P=0.001),and CD206(P=0.001) increased in the miR-204 mimic group. Conclusion The hUC-MSC exosomes overexpressing miR-204 can inhibit the polarization of macrophages in the I/R mouse model to M1-type and promote the polarization to M2-type.


Assuntos
Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Traumatismo por Reperfusão Miocárdica , Animais , Humanos , Camundongos , Modelos Animais de Doenças , Exossomos/metabolismo , Exossomos/patologia , Interleucina-10/metabolismo , Macrófagos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Osteogênese , Volume Sistólico , Fator de Necrose Tumoral alfa/metabolismo , Cordão Umbilical/metabolismo , Cordão Umbilical/patologia , Função Ventricular Esquerda
10.
Trop Anim Health Prod ; 54(6): 383, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36380247

RESUMO

Theileriosis is one of the top ten economically important diseases in cattle in India. Cytokines are considered important mediators and regulators of the immune response to an infection. In the present study, the gene expression profiles of fourteen cytokines (IL1A, IL1B, IL2, IL4, IL6, IL8, IL10, IL12A, IL12B, IL16, TGFB1, TNFA, IFNA and IFNB) were compared in Theileria annulata-infected and healthy crossbred cattle. Blood samples were obtained from the District Disease Diagnostic Laboratory, Karnal. The presence/absence of T. annulata infection in the animals was determined on the basis of blood smear examination and molecular detection through PCR using the genus-specific primers. Total RNA was extracted from peripheral blood mononuclear cells, which was further reverse transcribed to cDNA. Primer3 software was employed to design the primers for Real-Time qPCR. The results were examined using 2-∆∆Ct method with RPS15 and GAPDH as the reference genes. The expression of IL1B, IL6, IL8, IL10, IL12A, IL12B, TNFA, IFNA and IFNB was significantly higher, whereas the expression of IL2 was lower in the infected animals. The transcript levels of IL1A and TGFB1 were also higher in the diseased animals, but the results were non-significant. This study profiles the expression kinetics of various pro-inflammatory and anti-inflammatory cytokine genes in response to bovine theileriosis.


Assuntos
Doenças dos Bovinos , Theileria annulata , Theileria , Theileriose , Bovinos , Animais , Theileria annulata/genética , Leucócitos Mononucleares/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Interleucina-2/metabolismo , Interleucina-8 , Citocinas/genética , Citocinas/metabolismo , Primers do DNA
11.
Int J Mol Sci ; 23(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36362229

RESUMO

Oocyte development and fertilization are largely influenced by the microenvironment of the follicular fluid (FF), and the exploration of its molecular/metabolic composition may help in improving in vitro fertilization (IVF) outcomes. Here, the concentrations of molecules related to oxidative stress/inflammation were measured in FF from follicles at oocyte retrieval during IVF. Here, the FF antioxidant potential was correlated with the number of retrieved/mature oocytes and the number of fertilized ones. FF collected from the follicles of normal fertilized oocytes presented an elevated antioxidant capability, lower levels of pro-inflammatory molecules (i.e., IL-6, IL-8, IL-12, TGF-ß, and HIF-1α), and a higher IL-10 concentration. FF samples from follicles at oocyte retrieval that resulted in top-quality embryos displayed a peculiar antioxidant capability and a further decrease in proinflammatory molecules when compared with FF, giving rise to poor-quality embryos. Finally, pro-inflammatory molecules were lower and accompanied by a high antioxidant capability in samples giving rise to successful embryo implantation. The antioxidant capability and IL-10 displayed a good predictive ability for fertilization and embryo quality. Overall, our data showed the great influence of oxidative stress on the oocytes' fertilization, and shed light on the importance of controlling the inflammatory and oxidative status of FF to obtain good-quality embryos with significant implantation potential.


Assuntos
Antioxidantes , Interleucina-10 , Feminino , Animais , Interleucina-10/metabolismo , Antioxidantes/metabolismo , Oócitos/metabolismo , Líquido Folicular/metabolismo , Fertilização In Vitro/métodos , Estresse Oxidativo , Transdução de Sinais
12.
Int J Mol Sci ; 23(21)2022 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-36362383

RESUMO

The Human Mesenchymal Stem Cell (hMSC) secretome has pleiotropic effects underpinning its therapeutic potential. hMSC serum-free conditioned media (SFCM) contains a variety of cytokines, with previous studies linking a changed secretome composition to physoxia. The Jurkat T cell model allowed the efficacy of SFCM vs. serum-free media (SFM) in the suppression of immunological aspects, including proliferation and polarisation, to be explored. Cell growth in SFM was higher [(21% O2 = 5.3 × 105 ± 1.8 × 104 cells/mL) and (2% O2 = 5.1 × 105 ± 3.0 × 104 cells/mL)], compared to SFCM [(21% O2 = 2.4 × 105 ± 2.5 × 104 cells/mL) and (2% O2 = 2.2 × 105 ± 5.8 × 103 cells/mL)]. SFM supported IL-2 release following activation [(21% O2 = 5305 ± 211 pg/mL) and (2% O2 = 5347 ± 327 pg/mL)] whereas SFCM suppressed IL-2 secretion [(21% O2 = 2461 ± 178 pg/mL) and (2% O2 = 1625 ± 159 pg/mL)]. Anti-inflammatory cytokines, namely IL-4, IL-10, and IL-13, which we previously confirmed as components of hMSC SFCM, were tested. IL-10 neutralisation in SFCM restored proliferation in both oxygen environments (SFM/SFCM+antiIL-10 ~1-fold increase). Conversely, IL-4/IL-13 neutralisation showed no proliferation restoration [(SFM/SFM+antiIL-4 ~2-fold decrease), and (SFM/SFCM+antiIL-13 ~2-fold decrease)]. Present findings indicate IL-10 played an immunosuppressive role by reducing IL-2 secretion. Identification of immunosuppressive components of the hMSC secretome and a mechanistic understanding of their action allow for the advancement and refinement of potential future cell-free therapies.


Assuntos
Interleucina-10 , Células-Tronco Mesenquimais , Humanos , Interleucina-10/metabolismo , Células-Tronco Mesenquimais/metabolismo , Interleucina-13 , Interleucina-2 , Interleucina-4 , Secretoma , Imunomodulação , Meios de Cultura Livres de Soro , Citocinas
13.
Front Immunol ; 13: 1038332, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389843

RESUMO

Trypanosoma cruzi is the causative protozoan of Chagas' Disease, a neglected tropical disease that affects 6-7 million people worldwide. Interaction of the parasite with the host immune system is a key factor in disease progression and chronic symptoms. Although the human immune system is capable of controlling the disease, the parasite has numerous evasion mechanisms that aim to maintain intracellular persistence and survival. Due to the pronounced genetic variability of T. cruzi, co-infections or mixed infections with more than one parasite strain have been reported in the literature. The intermodulation in such cases is unclear. This study aimed to evaluate the co-infection of T. cruzi strains G and CL compared to their individual infections in human macrophages derived from THP-1 cells activated by classical or alternative pathways. Flow cytometry analysis demonstrated that trypomastigotes were more infective than extracellular amastigotes (EAs) and that strain G could infect more macrophages than strain CL. Classically activated macrophages showed lower number of infected cells and IL-4-stimulated cells displayed increased CL-infected macrophages. However, co-infection was a rare event. CL EAs decreased the production of reactive oxygen species (ROS), whereas G trypomastigotes displayed increased ROS detection in classically activated cells. Co-infection did not affect ROS production. Monoinfection by strain G or CL mainly induced an anti-inflammatory cytokine profile by decreasing inflammatory cytokines (IFN-γ, TNF-α, IL-1ß) and/or increasing IL-4, IL-10, and TGF-ß. Co-infection led to a predominant inflammatory milieu, with reduced IL-10 and TGF-ß, and/or promotion of IFN-γ and IL-1ß release. Infection by strain G reduced activation of intracellular signal transducer and activator of transcription (STAT) factors. In EAs, monoinfections impaired STAT-1 activity and promoted phosphorylation of STAT-3, both changes may prolong cell survival. Coinfected macrophages displayed pronounced activation of all STATs examined. These activations likely promoted parasite persistence and survival of infected cells. The collective results demonstrate that although macrophages respond to both strains, T. cruzi can modulate the intracellular environment, inducing different responses depending on the strain, parasite infective form, and co-infection or monoinfection. The modulation influences parasite persistence and survival of infected cells.


Assuntos
Doença de Chagas , Coinfecção , Trypanosoma cruzi , Humanos , Coinfecção/metabolismo , Interleucina-10/metabolismo , Interleucina-4/metabolismo , Macrófagos , Espécies Reativas de Oxigênio/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT6/metabolismo
14.
Mediators Inflamm ; 2022: 2054879, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405994

RESUMO

Atherosclerosis, which is characterized by chronic inflammation in the arterial wall, is driven by immune cells and cytokines. Recent evidence indicated that interleukin (IL)-27 showed pleiotropic properties in immune diseases. However, precise mechanisms of IL-27, especially in atherosclerosis remains unknown. In our research, we examined the influence of the administration of IL-27 and an anti-IL-27p28 antibody (anti-IL-27p28-Ab) on both the initiation and the progression of atherosclerosis. In the groups (both the initiation and the progression) receiving recombinant IL-27 administration, the formation of atherosclerotic plaques was suspended, and the percentage of regulatory T cells (LAP+ or Foxp3+) in the spleen and peripheral blood was increased. Meanwhile, the number of T helper 1 (Th1) and T helper 17 (Th17) cells was decreased. In the peripheral blood plasma, TGF-ß and IL-10 expression were increased, while the levels of IFN-γ and IL-17 were reduced. As for lesions, the mRNA expression of Foxp3, TGF-ß, and IL-10 was increased, while that of IFN-γ and IL-17 was reduced. In the anti-IL-27p28 antibody groups, we obtained opposite results. We also observed that DCs treated with IL-27 display a tolerogenic phenotype and that IL-27-treated tolerogenic DCs (tDCs) are likely to play a protective role during atherosclerosis. Our study indicates that IL-27 or adoptive transfer of IL-27 loaded tDCs may be a new therapeutic approach in atherosclerosis.


Assuntos
Aterosclerose , Interleucina-27 , Camundongos , Animais , Linfócitos T Reguladores/metabolismo , Interleucina-10/metabolismo , Interleucina-27/metabolismo , Interleucina-17/metabolismo , Apolipoproteínas E/genética , Aterosclerose/tratamento farmacológico , Interleucinas/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fatores Imunológicos/uso terapêutico , Fatores de Transcrição Forkhead/metabolismo , Células Dendríticas/metabolismo
15.
Vet Res ; 53(1): 87, 2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36273217

RESUMO

Muscle larvae of Trichinella spiralis parasitize the host intestinal epithelium. The mechanisms of exosomes participating in the invasion of T. spiralis muscle larvae are unclear. Hence, the purpose of this study was to explore the effect of exosomes derived from T. spiralis infective larvae (TsExos) on the barrier function of porcine small intestinal epithelial cells (IPEC-J2). First, TsExos were successfully obtained, and their ingestion by epithelial cells was validated. Furthermore, the optimal induction condition was determined by the CCK8 kit, and we found that exposure to 150 µg/mL TsExos for 12/24 h decreased the viability of IPEC-J2 cells by 30%. Based on this outcome, the effects of TsExos on cell biological processes and tight junctions were studied. After coincubation of TsExos and IPEC-J2 cells, the results showed a significant increase in the content of FITC-dextran and in the levels of lactate dehydrogenase (LDH) and reactive oxygen species (ROS). The rate of apoptosis increased by 12.57%, and nuclear pyknosis and nuclear rupture were observed. After the cells were induced by TsExos, the expression of IL-1 was upregulated, but the expression of IL-10, TGF-ß, TLR-5, MUC-1 and MUC-2 was downregulated. TsExo induction also led to a decrease in the levels of ZO-1, CLDN-3, and OCLN. In conclusion, TsExos are involved in several cellular biological processes, and they function by disrupting physiological and biochemical processes, hyperactivating innate immunity, and damaging tight junctions.


Assuntos
Exossomos , Trichinella spiralis , Suínos , Animais , Trichinella spiralis/fisiologia , Interleucina-10/metabolismo , Interleucina-10/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Receptor 5 Toll-Like/metabolismo , Mucosa Intestinal , Células Epiteliais/metabolismo , Larva/fisiologia , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Lactato Desidrogenases/metabolismo , Interleucina-1/metabolismo
16.
Biomed Res Int ; 2022: 9899135, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36277890

RESUMO

Aiming to reveal the role of ADCS-Exos in secretion of inflammatory factors, Th17 and regulatory T (Treg) cell differentiation from naïve CD4+ T cells in hypertrophic scaring formation and maturation is explored. ELISA, qRT-PCR, and immunoblotting are performed to assay the local inflammatory factors IL-6, IL-10, IL-17A, and TNF-α, and transcriptional factors of RORϒt and Foxp3, in scaring tissue from patients and mice wound models treated with or without ADCS-Exos. Immunohistochemistry staining and immunoblotting are conducted to assay the extracellular matrix (ECM) deposition in vitro and in vivo. The results show that IL-6, IL-10, IL-17A, TNF-α, RORϒt, and Foxp3 are increased on mRNA and protein levels in hypertrophic scaring compared with atrophic scaring and normal skin. Naïve CD4+ T cells treated with ADCS-Exos in vitro can produce significantly less IL-6, IL-17A, TNF-α, and RORϒt and more IL-10 and Foxp3 on mRNA and protein levels. In addition, mice in ADSC-Exos-treated group demonstrate less collagen deposition; decreased IL-17A, TNF-α, and RORϒt; and increased IL-10 and Foxp3 production.


Assuntos
Exossomos , Linfócitos T Reguladores , Camundongos , Animais , Linfócitos T Reguladores/metabolismo , Interleucina-17/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Exossomos/metabolismo , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Células-Tronco/metabolismo , RNA Mensageiro/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Colágeno/metabolismo
17.
Sci Rep ; 12(1): 17956, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36289354

RESUMO

Gangliogliomas (GGs) are low-grade brain tumours that cause intractable focal epilepsy in children and adults. In GG, as in epileptogenic focal malformations (i.e., tuberous sclerosis complex, TSC), there is evidence of sustained neuroinflammation with involvement of the pro-inflammatory cytokine IL-1ß. On the other hand, anti-inflammatory mediators are less studied but bear relevance for understanding seizure mechanisms. Therefore, we investigated the effect of the key anti-inflammatory cytokine IL-10 on GABAergic neurotransmission in GG. We assessed the IL-10 dependent signaling by transcriptomic analysis, immunohistochemistry and performed voltage-clamp recordings on Xenopus oocytes microtransplanted with cell membranes from brain specimens, to overcome the limited availability of acute GG slices. We report that IL-10-related mRNAs were up-regulated in GG and slightly in TSC. Moreover, we found IL-10 receptors are expressed by neurons and astroglia. Furthermore, GABA currents were potentiated significantly by IL-10 in GG. This effect was time and dose-dependent and inhibited by blockade of IL-10 signaling. Notably, in the same tissue, IL-1ß reduced GABA current amplitude and prevented the IL-10 effect. These results suggest that in epileptogenic tissue, pro-inflammatory mechanisms of hyperexcitability prevail over key anti-inflammatory pathways enhancing GABAergic inhibition. Hence, boosting the effects of specific anti-inflammatory molecules could resolve inflammation and reduce intractable seizures.


Assuntos
Epilepsia Resistente a Medicamentos , Ganglioglioma , Adulto , Criança , Humanos , Receptores de GABA-A/metabolismo , Ganglioglioma/complicações , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Receptores de Interleucina-10/metabolismo , Receptores Imunológicos/metabolismo , Ácido gama-Aminobutírico
18.
Drug Des Devel Ther ; 16: 3677-3689, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36277599

RESUMO

Background: Tumor microenvironment has attracted more and more attention in oncology. Alisol B23 acetate (AB23A) inhibits the proliferation of tumor cells including non-small cell lung cancer (NSCLC) cells. However, whether AB23A plays a role in the tumor microenvironment of NSCLC still remains obscure. Methods: After THP-1 cells were polarized to M0 type by PMA, M0 macrophages were differentiated into M1 by LPS and IFNγ, and were differentiated into M2 by IL-4 and IL-13. The differentiation of THP-1 cells was detected by flow cytometry. After AB23A was given to macrophage RT-qPCR and ELISA detected the expressions of IL-6, IL-1ß, IL-10 and TGF-ß. Western blot and RT-qPCR detected the expressions of CD11b and CD18 at both mRNA and protein levels. Lung cancer cell A549 cells were induced by above related macrophage culture medium. Cell proliferation was detected by CCK-8. Tunel, wound healing and Transwell detected the apoptotic, migration and invasion capabilities. Next, M0 and M1-type macrophages were cultured in the cell culture medium of conventional A549 cells, to which AB23A was added. Subsequently, cell differentiation and inflammatory response were measured. Finally, the expression of CD18 in A549 cells was knocked down to construct NSCLC tumor-bearing mice and AB23A was applied for intragastric administration. Immunohistochemistry detected the polarization of macrophages in tumor tissues. Western blot detected the expressions of CD11b, CD18, invasion-, migration- and apoptosis-related proteins. Results: AB23A promoted the polarization of macrophages towards M1, thus promoting the apoptosis and inhibiting the invasion and migration of A549 cells. The tumor cell culture medium induced M0 macrophages to M2, while AB23A reversed this effect. AB23A targeted CD11b/CD18 and improved the polarization of macrophages, thereby affecting tumor invasion, migration and apoptosis. Conclusion: AB23A affected the polarization of tumor-associated macrophages through the targeted regulation of CD11b/CD18, thus inhibiting the development of lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Colestenonas , Neoplasias Pulmonares , Animais , Camundongos , Carcinoma Pulmonar de Células não Pequenas/patologia , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-13/metabolismo , Interleucina-4/metabolismo , Interleucina-6/metabolismo , Neoplasias Pulmonares/patologia , Macrófagos , RNA Mensageiro/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Microambiente Tumoral , Colestenonas/farmacologia
19.
Nutrients ; 14(20)2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36296958

RESUMO

BACKGROUND: Inflammaging is considered to drive loss of muscle function. Omega-3 fatty acids exhibit anti-inflammatory properties. Therefore, we examined the effects of eight weeks of vibration and home-based resistance exercise combined with a whey-enriched, omega-3-supplemented diet on muscle power, inflammation and muscle biomarkers in community-dwelling old adults. METHODS: Participants were randomized to either exercise (3x/week, n = 20), exercise + high-protein diet (1.2-1.5 g/kg, n = 20), or exercise + high-protein and omega-3-enriched diet (2.2 g/day, n = 21). Muscle power (watt/m2) and chair rise test (CRT) time (s) were assessed via CRT measured with mechanography. Furthermore, leg strength (kg/m2) and fasting concentrations of inflammatory (interleukin (IL-) 6, IL-10, high-mobility group box-1 (HMGB-1)) and muscle biomarkers (insulin-like growth factor (IGF-) 1, IGF-binding protein-3, myostatin) were assessed. RESULTS: Sixty-one participants (70.6 ± 4.7 years; 47% men) completed the study. According to generalized linear mixed models, a high-protein diet improved leg strength and CRT time. Only IGF-1 increased with additional omega-3. Sex-specific analyses revealed that muscle power, IL-6, IL-6/IL-10 ratio, and HMGB-1 improved significantly in the male high-protein, omega-3-enriched group only. CONCLUSION: Vibration and home-based resistance exercise combined with a high-protein, omega-3-enriched diet increased muscle power and reduced inflammation in old men, but not in old women. While muscle biomarkers remained unchanged, a high-protein diet combined with exercise improved leg strength and CRT time.


Assuntos
Dieta Rica em Proteínas , Ácidos Graxos Ômega-3 , Treinamento de Força , Feminino , Humanos , Masculino , Biomarcadores/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Proteínas HMGB/metabolismo , Proteínas HMGB/farmacologia , Inflamação/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Força Muscular , Músculo Esquelético/metabolismo , Miostatina/metabolismo , Projetos Piloto , Vibração , Idoso
20.
Parasit Vectors ; 15(1): 393, 2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36303229

RESUMO

BACKGROUND: Women in early pregnancy infected by Toxoplasma gondii may have severe adverse pregnancy outcomes, such as spontaneous abortion and fetal malformation. The inhibitory molecule T cell immunoglobulin and mucin domain 3 (Tim-3) is highly expressed on decidual dendritic cells (dDCs) and plays an important role in maintaining immune tolerance. However, whether T. gondii infection can cause dDC dysfunction by influencing the expression of Tim-3 and further participate in adverse pregnancy outcomes is still unclear. METHODS: An abnormal pregnancy model in Tim-3-deficient mice and primary human dDCs treated with Tim-3 neutralizing antibodies were used to examine the effect of Tim-3 expression on dDC dysfunction after T. gondii infection. RESULTS: Following T. gondii infection, the expression of Tim-3 on dDCs was downregulated, those of the pro-inflammatory functional molecules CD80, CD86, MHC-II, tumor necrosis factor-α (TNF-α), and interleukin-12 (IL-12) were increased, while those of the tolerant molecules indoleamine 2,3-dioxygenase (IDO) and interleukin-10 (IL-10) were significantly reduced. Tim-3 downregulation by T. gondii infection was closely associated with an increase in proinflammatory molecules and a decrease in tolerant molecules, which further resulted in dDC dysfunction. Moreover, the changes in Tim-3 induced by T. gondii infection further reduced the secretion of the cytokine IL-10 via the SRC-signal transducer and activator of transcription 3 (STAT3) pathway, which ultimately contributed to abnormal pregnancy outcomes. CONCLUSIONS: Toxoplasma gondii infection can significantly downregulate the expression of Tim-3 and cause the aberrant expression of functional molecules in dDCs. This leads to dDC dysfunction, which can ultimately contribute to abnormal pregnancy outcomes. Further, the expression of the anti-inflammatory molecule IL-10 was significantly decreased by Tim-3 downregulation, which was mediated by the SRC-STAT3 signaling pathway in dDCs after T. gondii infection.


Assuntos
Células Dendríticas , Receptor Celular 2 do Vírus da Hepatite A , Toxoplasmose , Animais , Feminino , Humanos , Camundongos , Gravidez , Células Dendríticas/parasitologia , Células Dendríticas/patologia , Regulação para Baixo , Receptor Celular 2 do Vírus da Hepatite A/genética , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Toxoplasma , Toxoplasmose/imunologia
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