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1.
J Photochem Photobiol B ; 203: 111731, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31935633

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a progressive and chronic inflammatory disease with a poor prognosis and very few available treatment options. Low-level laser therapy (LLLT) has been gaining prominence as a new and effective anti-inflammatory and immunomodulatory agent. Can lung inflammation and the airway remodeling be regulated by LLLT in an experimental model of IPF in C57Bl/6 mice? The present study investigated if laser attenuates cellular migration to the lungs, the airway remodeling as well as pro-fibrotic cytokines secretion from type II pneumocytes and fibroblasts. Mice were irradiated (780 nm and 30 mW) and then euthanized fifteen days after bleomycin-induced lung fibrosis. Lung inflammation and airway remodeling were evaluated through leukocyte counting in bronchoalveolar lavage fluid (BALF) and analysis of collagen in lung, respectively. Inflammatory cells in blood were also measured. For in vitro assays, bleomycin-activated fibroblasts and type II pneumocytes were irradiated with laser. The pro- and anti-inflammatory cytokines level in BALF as well as cells supernatant were measured by ELISA, and the TGFß in lung was evaluated by flow cytometry. Lung histology was used to analyze collagen fibers around the airways. LLLT reduced both migration of inflammatory cells and deposition of collagen fibers in the lungs. In addition, LLLT downregulated pro-inflammatory cytokines and upregulated the IL-10 secretion from fibroblasts and pneumocytes. Laser therapy greatly reduced total lung TGFß. Systemically, LLLT also reduced the inflammatory cells counted in blood. There is no statistical difference in inflammatory parameters studied between mice of the basal group and the laser-treated mice. Data obtained indicate that laser effectively attenuates the lung inflammation, and the airway remodeling in experimental pulmonary fibrosis is driven to restore the balance between the pro- and anti-inflammatory cytokines in lung and inhibit the pro-fibrotic cytokines secretion from fibroblasts.


Assuntos
Remodelação das Vias Aéreas , Citocinas/metabolismo , Fibrose Pulmonar Idiopática/radioterapia , Lasers , Animais , Líquido da Lavagem Broncoalveolar/química , Células Cultivadas , Citocinas/análise , Modelos Animais de Doenças , Regulação para Baixo/efeitos da radiação , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Células Epiteliais/efeitos da radiação , Fibroblastos/citologia , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Fibrose Pulmonar Idiopática/patologia , Terapia a Laser , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regulação para Cima/efeitos da radiação
2.
Oral Dis ; 26(1): 200-212, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31571323

RESUMO

OBJECTIVES: This study evaluated the effects of type 2 diabetes mellitus (DM), smoking, and these two factors combined on gingival crevicular fluid levels and ratios of pro-/anti-inflammatory cytokines. Associations between cytokines with each other and with key periodontal pathogens in periodontal sites under the challenge of one or both of these risk factors were also assessed. METHODS: A total of 102 subjects with periodontitis were included in this cross-sectional study and assigned to one of the following groups: non-diabetic non-smokers (control group, n = 25), non-smokers with DM (DM group, n = 30), non-diabetic smokers (S group, n = 26), and smokers with DM (S + DM group, n = 21). The levels of 13 pro-inflammatory (IFN-γ, TNF-α, MIP-1α, GM-CSF, IL-1ß, IL-2, IL-6, IL-7, IL-8, IL-12, IL-17, IL-21, and IL-23) and 5 anti-inflammatory (IL-4, IL-5, IL-10, IL-13, and TGF-ß) cytokines were assessed in healthy and diseased sites, using multiplex immunoassay. Ratios of pro-/anti-inflammatory cytokines were obtained in all possible permutations. The levels of 7 key periodontal pathogens were evaluated by qPCR. RESULTS: Overall, the ratios of pro-/anti-inflammatory cytokines were higher in healthy and diseased sites of the DM group and in healthy sites of the S + DM group, and lower in diseased sites of the S group, compared with the control (p < .05). The proportion of the pro-inflammatory cytokines in relation to the 18 cytokines studied was higher in the DM group and lower in the S group, whereas the proportion of the anti-inflammatory cytokines was lower in both diabetic groups and higher in the S group, compared to the control (p < .05). A cluster of six common cytokines (IL-4, IL-5, IL-12, IL-13, IL-21, and IL-23) was observed in the diseased sites of all groups studied. Eight common cytokines (IL-4, IL-5, IL-12, IL-13, IL-17, IL-21, IL-23, and IFN-γ) grouped closely in the healthy sites of both diabetic groups. Significant associations between pathogens and cytokines occurred mainly in the diseased sites of the S + DM group (p < .05). CONCLUSION: Diabetes mellitus induced an overall pro-inflammatory state, while smoking mainly stimulated immunosuppression in periodontal sites. When the two risk factors overlapped, smoking seemed to partially assuage the hyperinflammatory effect of DM.


Assuntos
Periodontite Crônica/patologia , Diabetes Mellitus Tipo 2/complicações , Imunossupressão , Fumar , Adulto , Idoso , Estudos Transversais , Citocinas/análise , Feminino , Líquido do Sulco Gengival/química , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade
3.
Cell Mol Life Sci ; 77(1): 129-147, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31363816

RESUMO

Obesity is an endemic pathophysiological condition and a comorbidity associated with hypercholesterolemia, hypertension, cardiovascular disease, type 2 diabetes mellitus, and cancer. The adipose tissue of obese subjects shows hypertrophic adipocytes, adipocyte hyperplasia, and chronic low-grade inflammation. S100 proteins are Ca2+-binding proteins exclusively expressed in vertebrates in a cell-specific manner. They have been implicated in the regulation of a variety of functions acting as intracellular Ca2+ sensors transducing the Ca2+ signal and extracellular factors affecting cellular activity via ligation of a battery of membrane receptors. Certain S100 proteins, namely S100A4, the S100A8/S100A9 heterodimer and S100B, have been implicated in the pathophysiology of obesity-promoting macrophage-based inflammation via toll-like receptor 4 and/or receptor for advanced glycation end-products ligation. Also, serum levels of S100A4, S100A8/S100A9, S100A12, and S100B correlate with insulin resistance/type 2 diabetes, metabolic risk score, and fat cell size. Yet, secreted S100B appears to exert neurotrophic effects on sympathetic fibers in brown adipose tissue contributing to the larger sympathetic innervation of this latter relative to white adipose tissue. In the present review we first briefly introduce S100 proteins and then critically examine their role(s) in adipose tissue and obesity.


Assuntos
Tecido Adiposo/metabolismo , Obesidade/metabolismo , Proteínas S100/metabolismo , Tecido Adiposo/fisiopatologia , Animais , Citocinas/análise , Citocinas/metabolismo , Humanos , Inflamação/complicações , Inflamação/metabolismo , Inflamação/fisiopatologia , Macrófagos/metabolismo , Macrófagos/patologia , Obesidade/complicações , Obesidade/fisiopatologia , Proteínas S100/análise
4.
Braz Oral Res ; 33: e109, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800862

RESUMO

The objective of this study was to compare the periradicular responses in endodontic infections among members of two populations: an urban Brazilian population and a non-mixed indigenous population. Samples were collected immediately and 7 days after the cleaning and shaping procedures (after reducing the intracanal microbial load) in an attempt to characterize the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-9, interferon (IFN)-γ, IL-17, IL-10, and the chemokines CXCR4, CCL2/monocyte chemotactic protein (MCP)-1, and CCR6. The endogenous cytokine and chemokine expression levels were analyzed using real-time PCR. Only the urban population showed a significant increase in TNF-α, CCL2/MCP-1, CXCR4, and CCR6 expression following the cleaning and shaping of the root canal system. The IFN-γ levels were increased at the 2nd collection (p < 0.05) in the indigenous population. In turn, a significant increase in IL-10 and IL-17 expression (p < 0.05) was observed after the cleaning and shaping procedures (2nd collection) in both populations. No significant differences in the IL-1ß, IL-9, and CCL4 expression levels were observed between the 1st and 2nd collections in both populations. The results demonstrate a cytokine and chemokine expression profile that is specific to each analyzed population. However, immune modulation mediated by IL-10 began on the 7th day after the beginning of the endodontic treatment in both populations.


Assuntos
Necrose da Polpa Dentária/genética , Necrose da Polpa Dentária/imunologia , Periodontite Periapical/genética , Periodontite Periapical/imunologia , Brasil , Citocinas/análise , Regulação da Expressão Gênica , Humanos , Fenômenos do Sistema Imunológico , Índios Sul-Americanos , RNA Mensageiro/análise , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Tratamento do Canal Radicular/métodos , Estatísticas não Paramétricas , Fatores de Tempo , População Urbana
5.
BMC Complement Altern Med ; 19(1): 369, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842843

RESUMO

BACKGROUND: Bletilla striata is a traditional Chinese medicine used to treat hemorrhage, scald, gastric ulcer, pulmonary diseases and inflammations. In this study, we investigated bioactivity of the effective fraction of B. striata (EFB) in reducing the inflammatory cytokine production induced by water or organic extracts of PM2.5. METHODS: PM2.5 extracts were collected and analyzed by chromatographic system and inductively coupled plasma mass spectrometer. Cell viability was measured using MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay, and cell supernatant was analyzed by flow cytometry, ELISA, and qRT-PCR in cultured mouse macrophage cell line RAW264.7 treated with EFB and PM2.5 extracts. Expressions of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathway were measured by Western blot. RESULTS: PM2.5 composition is complex and the toxicity of PM2.5 extracts were not noticeable. The treatment of EFB at a wide dose-range of 0-40 µg/mL did not cause significant change of RAW264.7 cell proliferation. EFB pretreatment decreased the inflammatory cytokines in the macrophage. Further analysis showed that EFB significantly attenuated PM2.5-induced proinflammatory protein expression and downregulated the levels of phosphorylated NF-κBp65, inhibitor of kappa B (IκB)-α, c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38. CONCLUSIONS: Our study demonstrated the potential effectiveness of B. striata extracts for treating PM2.5-triggered pulmonary inflammation.


Assuntos
Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Orchidaceae , Material Particulado/toxicidade , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/química , Sobrevivência Celular/efeitos dos fármacos , Citocinas/análise , Citocinas/genética , Inflamação/metabolismo , Camundongos , Modelos Imunológicos , Extratos Vegetais/química , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transdução de Sinais/imunologia
6.
Medicine (Baltimore) ; 98(52): e18465, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876730

RESUMO

This study aimed to investigate the correlation of long noncoding RNA zinc finger antisense 1 (lncRNA ZFAS1) expression with disease risk, disease severity and inflammatory cytokines levels in lumbar disc degeneration (LDD) patients.83 LDD patients underwent surgery and 28 traumatized, non-LDD patients underwent lumbar disc surgery (controls) were consecutively enrolled in this case-control study. Lumbar disc tissue was obtained during surgery and herniated nucleus pulposus (HNP) was isolated to detect lncRNA ZFAS1 expression and inflammatory cytokines mRNA levels by RT-qPCR, and determine protein levels of inflammatory cytokines by western blot.HNP lncRNA ZFAS1 expression in LDD patients was up-regulated compared with controls (P < .001), and receiver operating characteristic (ROC) curve showed lncRNA ZFAS1 expression disclosed a good predictive value for LDD risk with area under curve (AUC) 0.753 (95% CI 0.646-0.859). And after adjustment by age, gender and body mass index (BMI), lncRNA ZFAS1 (P = .017) remained to be an independent predictive factor for higher LDD risk. In addition, lncRNA ZFAS1 expression was positively associated with Modified Pfirrmann Grade (P = .015). As to inflammatory cytokines, lncRNA ZFAS1 expression was observed to be positively correlated with TNF-α (P = .002), IL-1ß (P = .007) and IL-6 (P = .015) mRNAs expressions while reversely associated with IL-10 mRNA level (P = .014); and lncRNA ZFAS1 expression was also positively correlated with protein levels of TNF-α (P = .038) and IL-6 (P = .027) while reversely associated with IL-10 protein expression (P = .039).lncRNA ZFAS1 expression associates with increased risk, elevated disease severity and higher inflammatory cytokines levels in LDD patients.


Assuntos
Citocinas/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Deslocamento do Disco Intervertebral/metabolismo , Disco Intervertebral/metabolismo , Vértebras Lombares , RNA Antissenso/metabolismo , RNA Longo não Codificante/metabolismo , Adulto , Biomarcadores/análise , Western Blotting , Estudos de Casos e Controles , Citocinas/análise , Feminino , Humanos , Interleucina-10/análise , Interleucina-10/metabolismo , Interleucina-1beta/análise , Interleucina-1beta/metabolismo , Interleucina-6/análise , Interleucina-6/metabolismo , Disco Intervertebral/química , Masculino , Pessoa de Meia-Idade , RNA Longo não Codificante/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/metabolismo
7.
J Med Microbiol ; 68(12): 1802-1812, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31702539

RESUMO

Introduction. Candida albicans is responsible for several types of oral and systemic infections. In light of emerging resistance to antifungals, studies have demonstrated the antifungal effect of lactoferrin (LF), which is part of the innate immune system, has anticandidal activities.Methodology. C. albicans (2×106 c.f.u. ml-1) were incubated either with PBS or human LF (hLF) (100 µg ml-1) at 37 °C for 24 h and then RNA was isolated and virulence factors analysed. C. albicans (1×105 c.f.u.) was injected into the tail vein of immunocompromised wild-type and Ltf -/-. Then, 24 h later, the Ltf -/-I mice received hLF intravenously (100 µg g-1 body weight), while the control group received PBS. Then, 48 h later, the organs were collected, homogenized and C. albicans c.f.u.s were counted. In addition, the inflammatory mediators of kidneys and the virulence factors of C. albicans were analysed.Results. hLF-treated Ltf -/-I mice showed significant clearance of C. albicans in different organ tissues when compared to untreated Ltf -/-I mice. The inflammatory cytokines, such as IL-1ß, IL-6 , TNF-α and MPO and iNOS were downregulated in hLF-treated Ltf -/-I mice when compared to untreated Ltf -/-I mice. Whereas, IL-10 and IL-17A were upregulated at 72 h post infection when compared to Ltf -/-C mice. Histological analysis also revealed a significant decrease in the size and number of infectious foci in the hLF-treated groups. hLF treatment significantly downregulated several virulence factors of C. albicans both in vitro and in vivo.Conclusion. We concluded that hLF-treated Ltf -/- mice can reduce the severity of C. albicans-induced systemic infection.


Assuntos
Candidíase/tratamento farmacológico , Lactoferrina/uso terapêutico , Animais , Aderência Bacteriana , Candida albicans/fisiologia , Candidíase/imunologia , Candidíase/patologia , Citocinas/análise , Humanos , Rim/microbiologia , Rim/patologia , Lactoferrina/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
8.
Anticancer Res ; 39(11): 6403-6412, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704874

RESUMO

BACKGROUND: Cytokines, metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) take part in many processes involved in tumor progression and invasion such as degradation of the extracellular matrix, influence on immune cells associated with tumor tissue, and angiogenesis. Thus, the aim of this study was to compare the concentration of plasma levels and tissue expression of macrophage colony-stimulating factor (M-CSF), vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMP)-2 and MMP9, and their tissue inhibitors TIMP1 and TIMP2 in patients with cervical cancer, patients with high-grade cervical intraepithelial dysplasia (CIN3) and patients with ectropion. PATIENTS AND METHODS: Concentration and expression of all tested parameters was measured in serum with enzyme-linked immunosorbent assay (ELISA) and in tissue with immunohistochemistry method. RESULTS: The epithelial expression of M-CSF and TIMP1 in cancer tissue was much stronger as compared to that in ectropion and CIN3. In the case of MMP2, lack of or weak expression in epithelial cells was observed in all tested groups. Our studies showed statistical differences of tested parameters in tissue expression and in plasma concentrations in patients with cervical cancer, patients with CIN3 and patients with ectropion. Moreover, data revealed positive correlation between plasma level and cervical cancer cell expression of VEGF. CONCLUSION: Our findings indicate a potential role of all the proteins tested here in cervical cancer diagnosis, especially VEGF. However, further studies will show whether they play a role in the progression of cancerous changes in epithelial tissue of the cervix.


Assuntos
Fator Estimulador de Colônias de Macrófagos/análise , Metaloproteases/análise , Inibidores Teciduais de Metaloproteinases/análise , Displasia do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/química , Fator A de Crescimento do Endotélio Vascular/análise , Adenocarcinoma/sangue , Adenocarcinoma/química , Adulto , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/química , Citocinas/análise , Citocinas/sangue , Feminino , Humanos , Fator Estimulador de Colônias de Macrófagos/sangue , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 9 da Matriz/análise , Metaloproteinase 9 da Matriz/sangue , Metaloproteases/sangue , Pessoa de Meia-Idade , Inibidor Tecidual de Metaloproteinase-1/análise , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidor Tecidual de Metaloproteinase-2/análise , Inibidor Tecidual de Metaloproteinase-2/sangue , Inibidores Teciduais de Metaloproteinases/sangue , Displasia do Colo do Útero/sangue , Neoplasias do Colo do Útero/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto Jovem
9.
Acta Cir Bras ; 34(9): e201900902, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31778524

RESUMO

PURPOSE: To investigate the role of vagus nerve activation in the protective effects of hypercapnia in ventilator-induced lung injury (VILI) rats. METHODS: Male Sprague-Dawley rats were randomized to either high-tidal volume or low-tidal volume ventilation (control) and monitored for 4h. The high-tidal volume group was further divided into either a vagotomy or sham-operated group and each surgery group was further divided into two subgroups: normocapnia and hypercapnia. Injuries were assessed hourly through hemodynamics, respiratory mechanics and gas exchange. Protein concentration, cell count and cytokines (TNF-α and IL-8) in bronchoalveolar lavage fluid (BALF), lung wet-to-dry weight and pathological changes were examined. Vagus nerve activity was recorded for 1h. RESULTS: Compared to the control group, injurious ventilation resulted in a decrease in PaO2/FiO2 and greater lung static compliance, MPO activity, enhanced BALF cytokines, protein concentration, cell count, and histology injury score. Conversely, hypercapnia significantly improved VILI by decreasing the above injury parameters. However, vagotomy abolished the protective effect of hypercapnia on VILI. In addition, hypercapnia enhanced efferent vagus nerve activity compared to normocapnia. CONCLUSION: These results indicate that the vagus nerve plays an important role in mediating the anti-inflammatory effect of hypercapnia on VILI.


Assuntos
Líquido da Lavagem Broncoalveolar/química , Hipercapnia , Nervo Vago/cirurgia , Lesão Pulmonar Induzida por Ventilação Mecânica/prevenção & controle , Animais , Citocinas/análise , Modelos Animais de Doenças , Interleucina-8/análise , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/análise , Vagotomia
10.
Vet Parasitol ; 276: 108976, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31739256

RESUMO

Cutaneous leishmaniosis (CL) is a parasitic disease in animals and human with no satisfactory treatments and vaccination. Rapamycin is a potent inhibitor of mammalian target of rapamycin (mTOR) with various applications. Here, the effect of rapamycin alone or in combination with two other drugs, namely amphotericin B (AmB) and glucantime, was investigated against Leishmania tropica infection. In vitro viability and electron microscopy evaluation of the parasites showed detrimental changes in their appearance and viability. Treatment with clinically relevant dose of rapamycin (10.2 µg/dose) is able to control the parasite load in BALB/c mice infected with L. tropica. Furthermore, the cytokine profiles showed significant polarization towards Th1 immune response. Surprisingly, combination therapy with either AmB or glucantime was not efficient. Rapamycin is showed an effective alternative therapy against leishmaniosis caused by L. tropica.


Assuntos
Antiprotozoários/uso terapêutico , Leishmania tropica/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Sirolimo/uso terapêutico , Anfotericina B/farmacologia , Anfotericina B/uso terapêutico , Animais , Antiprotozoários/farmacologia , Linhagem Celular Tumoral , Citocinas/análise , Feminino , Humanos , Concentração Inibidora 50 , Leishmania tropica/crescimento & desenvolvimento , Leishmania tropica/ultraestrutura , Leishmaniose Cutânea/prevenção & controle , Linfonodos/parasitologia , Antimoniato de Meglumina/farmacologia , Antimoniato de Meglumina/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Carga Parasitária , Distribuição Aleatória , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/efeitos dos fármacos
11.
An Bras Dermatol ; 94(4): 434-441, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31644616

RESUMO

BACKGROUND: In-vitro studies showed that Leucine-rich glioma inactivated 3 (LGI3) is a keratinocyte-derived cytokine that stimulates melanin synthesis and is increased after ultra violet B (UVB) irradiation. So, we postulated that LGI3 may be involved in vitiligo aetiopathogenesis and may participate in narrow band ultra violet B (NB-UVB) induced pigmentation in vitiligo. OBJECTIVES: To assess this hypothesis, lesional LGI3 immunohistochemical expression of vitiligo patients before and after NB-UVB phototherapy was studied, and its correlation with repigmentation was evaluated. METHODS: Forty vitiligo patients and 20 age, sex, and skin phenotype-matched controls were enrolled. Patients were treated with NB-UVB thrice weekly for 12 weeks. VASI score was evaluated before and after NB-UVB sessions. For vitiligo patients, baseline LGI3 immunohistochemical staining was estimated, and compared to that of controls and to its post-treatment data in those patients. Results: Baseline LGI3 immunohistochemical studied parameters (expression, intensity, percentage and H score) were significantly lower in vitiligo cases than controls (p=0.003, 0.013, 0.001 and 0.001 respectively). After 12 weeks of NB-UVB phototherapy, these LGI3 immunohistochemical parameters were up-regulated and became comparable to that of controls (p >0.05 for all). There was a significant positive correlation between the improvement of both VASI score and LGI3 H score mean values (r=-0.349 , p=0.027). STUDY LIMITATIONS: Small number of investigated subjects. CONCLUSIONS: Decreased LGI3 protein may play an active role in vitiligo pathogenesis and its up-regulation after NB-UVB phototherapy, may actively participate in NB-UVB photo-induced melanogenesis.


Assuntos
Citocinas/análise , Proteínas/análise , Terapia Ultravioleta/métodos , Vitiligo/patologia , Vitiligo/radioterapia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Feminino , Humanos , Imuno-Histoquímica , Queratinócitos/efeitos da radiação , Masculino , Melanócitos/efeitos da radiação , Pessoa de Meia-Idade , Valores de Referência , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
12.
J Appl Oral Sci ; 27: e20180476, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31596364

RESUMO

OBJECTIVES: Miniscrew has been frequently used, considering that anchorage control is a critical point in orthodontic treatment, and its failure, the main adverse problem. Using two groups of stable (successful) and unstable (failed) mini-implants, this in vivo study aimed to quantify proinflammatory cytokines IL-1 α, IL-6, IL-17, and TNF-α and osteoclastogenesis marker RANK, RANKL, and OPG in gingival tissue, using the real-time polymerase chain reaction technique. METHODOLOGY: Thirteen patients of both sexes (11-49 years old) under orthodontic treatment were selected, obtaining 11 successful and 7 failed mini-implants. The mini-implants were placed and removed by the same surgeon, in both jaws. The mean time of permanence in the mouth was 29.4 months for successful and 7.6 months for failed mini-implants. At removal time, peri-mini-implant gingival tissue samples were collected and processed for quantification of the proinflammatory cytokines and osteoclastogenesis markers. Nonparametric Wilcoxon rank-sum test considering the clusters and Kruskal-Wallis test were used for statistical analysis (α=0.05). RESULTS: No significant difference (p>0.05) was observed between the groups for either quantification of cytokines or osteoclastogenesis markers, except for IL-6 (p<0.05). CONCLUSIONS: It may be concluded that the expression of IL-1α, IL-17, TNF-α, RANK, RANKL, and OPG in peri-implant gingival tissue were not determinant for mini-implant stability loss, but the higher IL-6 expression could be associated with mini-implant failure.


Assuntos
Citocinas/análise , Implantes Dentários/efeitos adversos , Gengivite/patologia , Procedimentos de Ancoragem Ortodôntica/efeitos adversos , Osteogênese/fisiologia , Peri-Implantite/patologia , Adolescente , Adulto , Perda do Osso Alveolar , Biomarcadores/análise , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoprotegerina/análise , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
13.
Infect Immun ; 88(1)2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31611276

RESUMO

Pseudomonas aeruginosa is an opportunistic pathogen that is a common cause of nosocomial infections. The molecular mechanisms governing immune responses to P. aeruginosa infection remain incompletely defined. Early growth response 1 (Egr-1) is a zinc-finger transcription factor that controls inflammatory responses. Here, we characterized the role of Egr-1 in host defense against P. aeruginosa infection in a mouse model of acute bacterial pneumonia. Egr-1 expression was rapidly and transiently induced in response to P. aeruginosa infection. Egr-1-deficient mice displayed decreased mortality, reduced levels of proinflammatory cytokines (tumor necrosis factor [TNF], interleukin-1ß [IL-1ß], IL-6, IL-12, and IL-17), and enhanced bacterial clearance from the lung. Egr-1 deficiency caused diminished NF-κB activation in P. aeruginosa-infected macrophages independently of IκBα phosphorylation. A physical interaction between Egr-1 and NF-κB p65 was found in P. aeruginosa-infected macrophages, suggesting that Egr-1 could be required for assembly of heterodimeric transcription factors that direct synthesis of inflammatory mediators. Interestingly, Egr-1 deficiency had no impact on neutrophil recruitment in vivo due to its differential effects on chemokine production, which included diminished accumulation of KC (CXCL1), MIP2 (CXCL2), and IP-10 (CXCL10) and increased accumulation of LIX (CXCL5). Importantly, Egr-1-deficient macrophages and neutrophils displayed significant increases in nitric oxide production and bacterial killing ability that correlated with enhanced bacterial clearance in Egr-1-deficient mice. Together, these findings suggest that Egr-1 plays a detrimental role in host defense against P. aeruginosa acute lung infection by promoting systemic inflammation and negatively regulating the nitric oxide production that normally assists with bacterial clearance.


Assuntos
Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Pulmão/microbiologia , Pulmão/patologia , Pneumonia Bacteriana/imunologia , Infecções por Pseudomonas/imunologia , Pseudomonas aeruginosa/imunologia , Animais , Citocinas/análise , Modelos Animais de Doenças , Proteína 1 de Resposta de Crescimento Precoce/deficiência , Fatores Imunológicos/análise , Camundongos , Análise de Sobrevida
14.
Exp Parasitol ; 206: 107767, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31520603

RESUMO

Schistosoma mansoni eggs can influence immune responses directed at them, and the mechanisms by which this is achieved are being unravelled. Going towards, developing effective tools for the study of how S. mansoni influences naïve T cells, we have developed S. mansoni eggs expressing chicken ovalbumin (OVA), using a lentiviral transduction system. Indeed, such a parasite could be used in conjunction with cells from OT-II transgenic mice as a source of naïve, antigen-specific T cells. The expression of the transgenic protein was confirmed by real-time RT-PCR of OVA-specific mRNA and western blotting using polyclonal antibodies specific for OVA. T cells from OT-II transgenic mice expressing a T cell receptor specific for the OVA323-339 peptide recognised the OVA-transduced S. mansoni eggs. Using flow cytometry on CFSE-labelled OT-II splenocytes, we demonstrated that OVA-transduced eggs elicit higher OT-II proliferative responses than untransduced eggs. The OT-II T cells also produced TNF-α and IFN-γ following exposure to OVA-transduced eggs. In addition, moderate amounts of IL-6 and IL-17A were also detected. In contrast, no IL-10, IL-4 and IL-2 were detected in cultures, whether the cells were stimulated with transduced or untransduced eggs. Thus, the cytokine signatures showed the transfected eggs induced predominantly a Th1 response, with a small amount of IL-6 and IL-17.


Assuntos
Ovalbumina/análise , Receptores de Antígenos de Linfócitos T/imunologia , Schistosoma mansoni/metabolismo , Linfócitos T/imunologia , Animais , Western Blotting , Galinhas , Citocinas/análise , Citocinas/metabolismo , Eletroforese em Gel de Ágar , Feminino , Citometria de Fluxo , Interleucina-17/análise , Interleucina-17/metabolismo , Interleucina-2/análise , Interleucina-2/metabolismo , Interleucina-6/análise , Interleucina-6/metabolismo , Fígado/parasitologia , Linfonodos/citologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Ovalbumina/genética , Ovalbumina/imunologia , Ovalbumina/metabolismo , Óvulo/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Antígenos de Linfócitos T/genética , Transcrição Reversa , Schistosoma mansoni/genética , Schistosoma mansoni/crescimento & desenvolvimento , Baço/citologia , Linfócitos T/citologia
15.
Braz Oral Res ; 33: e040, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31508724

RESUMO

The study characterizes dental implant surfaces treated with phosphoric acid to assess the effects of acid treatment on blood cells and correlate them with cytokine levels. The implant surfaces examined were divided into untreated metal surface (US; n = 50), metal surface treated with phosphoric acid (ATS; n = 50) and cement surface (CS; n = 50) groups. The samples were characterized by scanning electron microscopy (SEM) and rheometry. The implants were incubated with human blood mononuclear cells for 24 h, with surface rinsing in the ATS treatment. Cell viability was determined by colorimetric methods and cytokines in the culture supernatant were quantified using flow cytometry. In the ATS group, the surface porosity and contact surface were increased and plaques were observed on the surface. The blood flow and viscosity curves were similar among the treatments, and the high cell viability rates indicate the biocompatibility of the materials used. An increase in the levels of IL-2, IL-4, IL-6, IL-10 and TNF-α was observed in the ATS and CS groups. There were positive correlations between IL-10 and IL-2 levels and between IL-10 and IL-4 levels in the culture supernatant of the ATS group. The results suggest that implant surface treatment with phosphoric acid activates the production of inflammatory cytokines. The increased cytokine levels can modulate the immune response, thereby improving biofunctional processes and promoting the success of dental implants.


Assuntos
Citocinas/análise , Implantes Dentários , Materiais Dentários/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Ácidos Fosfóricos/farmacologia , Anti-Inflamatórios , Sobrevivência Celular , Citocinas/metabolismo , Cimentos Dentários , Humanos , Interleucina-10/análise , Interleucina-10/metabolismo , Microscopia Eletrônica de Varredura , Reologia , Propriedades de Superfície
16.
J Appl Oral Sci ; 27: e20180671, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31508795

RESUMO

OBJECTIVE: To monitor early periodontal disease progression and to investigate clinical and molecular profile of inflamed sites by means of crevicular fluid and gingival biopsy analysis. METHODOLOGY: Eighty-one samples of twenty-seven periodontitis subjects and periodontally healthy individuals were collected for the study. Measurements of clinical parameters were recorded at day -15, baseline and 2 months after basic periodontal treatment aiming at monitoring early variations ofthe clinical attachment level. Saliva, crevicular fluid and gingival biopsies were harvested from clinically inflamed and non-inflamed sites from periodontal patients and from control sites of healthy patients for the assessment of IL-10, MMP-8, VEGF, RANKL, OPG and TGF-ß1 protein and gene expression levels. RESULTS: Baseline IL-10 protein levels from inflamed sites were higher in comparison to both non-inflamed and control sites (p<0.05). Higher expression of mRNA for IL-10, RANK-L, OPG, e TGF-ß1 were also observed in inflamed sites at day -15 prior treatment (p<0.05). After the periodontal treatment and the resolution of inflammation, seventeen percent of evaluated sites still showed clinically detectable attachment loss without significant differences in the molecular profile. CONCLUSIONS: Clinical attachment loss is a negative event that may occur even after successful basic periodontal therapy, but it is small and limited to a small percentage of sites. Elevated inflammation markers of inflamed sites from disease patients reduced to the mean levels of those observed in healthy subjects after successful basic periodontal therapy. Significantly elevated both gene and protein levels of IL-10 in inflamed sites prior treatment confirms its modulatory role in the disease status.


Assuntos
Perda da Inserção Periodontal/patologia , Periodontite/patologia , Adulto , Biomarcadores/análise , Biópsia , Estudos de Casos e Controles , Citocinas/análise , Feminino , Gengiva/patologia , Líquido do Sulco Gengival/química , Humanos , Masculino , Metaloproteinase 8 da Matriz/análise , Pessoa de Meia-Idade , Osteoprotegerina/análise , Periodontite/terapia , Reação em Cadeia da Polimerase em Tempo Real , Saliva/química , Estatísticas não Paramétricas , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/análise
17.
Food Funct ; 10(9): 6098-6109, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31495848

RESUMO

Hypercholesterolemia is a major risk factor for cardiovascular disease (CVD). Probiotics are one of the most popular dietary supplements for hypercholesterolemia, but there are questions as to whether there are differences between probiotics and cholesterol-lowering drugs like atorvastatin (ATO) both in effectiveness and in the underlying mechanisms. In this study, the hypocholesterolemia effects of 4 probiotic strains were investigated and compared with ATO, focusing on their impacts on the gut microbiota. A hypercholesterolemia model was established via high-fat diet (HFD) in golden hamsters after which ATO and the 4 probiotics were orally administered individually for 8 weeks. All probiotics were effective, but less than ATO, on body weight, serum parameters (TG, TC, LDL, INS, HbA1c) and expression of inflammatory factors (INF-α, IL-1ß, CRP), with strain JQII-5 being most significant. Besides, these effects were associated with restoration of microbiota dysbiosis induced by HFD. It was worth noting that ATO and probiotics induced different shifts of the gut microbiota in both structure and key phylotypes. Most interestingly, Allobaculum, a HFD-suppressed genus, reported to be involved in alleviating oxidative stress, was enriched by all tested probiotic strains, but not by ATO. Furthermore, Prevotella, also a HFD-suppressed genus, was uniquely reversed by JQII-5. Importantly, most of the alerted genera and reversed genera were found to be correlated with the inflammatory state and serum lipid level. Compared with ATO, the probiotic strains were less effective on body weight, hypercholesterolemia, and inflammation. However, probiotics exert additional favorable effects on the gut microbiota, making them excellent potential complements to cholesterol-lowering drugs like ATO.


Assuntos
Atorvastatina/uso terapêutico , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/fisiologia , Hipercolesterolemia/terapia , Lactobacillus plantarum/fisiologia , Pediococcus/fisiologia , Animais , Anticolesterolemiantes/uso terapêutico , Bactérias/classificação , Bactérias/isolamento & purificação , Cricetinae , Citocinas/análise , Disbiose/etiologia , Disbiose/terapia , Fezes/microbiologia , Glucose/metabolismo , Hipercolesterolemia/tratamento farmacológico , Masculino , Mesocricetus , Pediococcus acidilactici/fisiologia , Pediococcus pentosaceus/fisiologia , Probióticos/uso terapêutico , Ganho de Peso/efeitos dos fármacos
18.
Klin Lab Diagn ; 64(8): 484-489, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31479604

RESUMO

The aim of research was to evaluate the effectiveness of the effect of eradication therapy on the cytokine status of gastric juice in patients with chronic non-atrophic gastritis (CNG) and duodenal ulcer (DU) associated with Helicobacter pylori. Clinical observations and laboratory-instrumental studies performed in 95 patients aged 20 to 55 years with CNG and duodenal ulcer with determination of cytokine content of IL-1ß, IL-6 and TNF-α in the fasting portion of gastric juice. The most pronounced decrease in the content of proinflammatory cytokines in gastric juice on the background of treatment was found in patients of the 1st group who received combined therapy according to the scheme omeprazole + clarithromycin + amoxicillin. Analysis of the content of proinflammatory cytokines (IL-1ß, IL-6 and TNF-α) in gastric juice in patients with acute exacerbation showed that their concentration in all 8 patients after the course of therapy exceeded the norm (P < 0.05) and was IL -1ß - 30,30 + 1,15 pg/l, IL-6 - 10,4 + 0,83 pg / l and TNF-α - 32,5 + 1,13 pg / l. At the same time, the level of proinflammatory cytokines in gastric juice correlated with the degree of dissemination of H. pylori in the mucosa of the gastroduodenal zone. Helicobacter pylori infection in inflammation and ulceration in the mucous membrane of the stomach and duodenum, possibly in addition to other mechanisms, affects the activation of pro-inflammatory cytokines (IL-1beta, IL-6, TNF-alpha) in gastric juice. Incomplete eradication of H. Pylori after treatment during clinical endoscopic remission in patients with duodenal ulcer in the vast majority of cases is accompanied by the preservation of an increased level of pro-inflammatory cytokines in gastric juice, which may be one of the reasons for the relapse of the disease.


Assuntos
Citocinas/análise , Suco Gástrico/química , Gastrite/terapia , Infecções por Helicobacter/terapia , Adulto , Mucosa Gástrica , Gastrite/microbiologia , Helicobacter pylori , Humanos , Pessoa de Meia-Idade , Adulto Jovem
19.
Cell Biochem Funct ; 37(7): 464-473, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31396989

RESUMO

We sought to explore the functions and modulated factors of NOD1 in normal decidual stromal cells (DSCs) derived from the first trimester pregnancy and whether existed different expression of NOD1 between normal and unexplained recurrent pregnancy loss (URPL) in DSCs. Twenty-six patients with normal pregnancies that required abortion and 12 URPL patients at first trimester were enrolled for the study. As a result, we found lower levels of NOD1 in the DSCs derived from URPL compared with those from normal early trimester pregnancy. Furthermore, increased NOD1 expression in the normal DSCs induced apoptosis and increased monocyte chemotactic protein-1 (MCP-1) and IL-1ß (interleukin 1 beta) secretion but decreased their invasion capacity. In addition, several cytokines such as IL-1ß, tumour necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin-17 (IL-17) were present at the maternal-fetal interface in RPL and were found to regulate NOD1 expression in primary DSCs. Our study indicates that RPL may be associated with NOD1 aberrant expression in DSCs, which plays a significant role in maintaining pregnancy via infection control and regulation of immune responses that might affect the pregnancy outcome. We expect that our results will bring more comprehensively understanding about the connection between NOD1 and RPL for researchers.


Assuntos
Decídua/metabolismo , Proteína Adaptadora de Sinalização NOD1/metabolismo , Primeiro Trimestre da Gravidez/metabolismo , Células Estromais/metabolismo , Adulto , Apoptose/efeitos dos fármacos , Células Cultivadas , Citocinas/análise , Citocinas/metabolismo , Decídua/citologia , Decídua/efeitos dos fármacos , Ácido Diaminopimélico/análogos & derivados , Ácido Diaminopimélico/farmacologia , Feminino , Humanos , Proteína Adaptadora de Sinalização NOD1/genética , Gravidez , Primeiro Trimestre da Gravidez/efeitos dos fármacos , Células Estromais/efeitos dos fármacos
20.
PLoS Negl Trop Dis ; 13(8): e0007650, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31412039

RESUMO

Enteric fevers, caused by the Salmonella enterica serovars Typhi (ST), Paratyphi A (PA) and Paratyphi B (PB), are life-threatening illnesses exhibiting very similar clinical symptoms but with distinct epidemiologies, geographical distributions and susceptibilities to antimicrobial treatment. Nevertheless, the mechanisms by which the host recognizes pathogens with high levels of homology, such as these bacterial serovars, remain poorly understood. Using a three-dimensional organotypic model of the human intestinal mucosa and PA, PB, and ST, we observed significant differences in the secretion patterns of pro-inflammatory cytokines and chemokines elicited by these serovars. These cytokines/chemokines were likely to be co-regulated and influenced the function of epithelial cells, such as the production of IL-8. We also found differing levels of polymorphonuclear leukocyte (PMN) migration among various infection conditions that either included or excluded lymphocytes and macrophages (Mϕ), strongly suggesting feedback mechanisms among these cells. Blocking experiments showed that IL-1ß, IL-6, IL-8, TNF-α and CCL3 cytokines were involved in the differential regulation of migration patterns. We conclude that the crosstalk among the lymphocytes, Mϕ, PMN and epithelial cells is cytokine/chemokine-dependent and bacterial-serotype specific, and plays a pivotal role in orchestrating the functional efficiency of the innate cells and migratory characteristics of the leukocytes.


Assuntos
Comunicação Celular , Leucócitos/imunologia , Salmonella paratyphi A/imunologia , Salmonella paratyphi B/imunologia , Salmonella typhi/imunologia , Febre Tifoide/imunologia , Movimento Celular , Citocinas/análise , Células Epiteliais/imunologia , Humanos , Mucosa Intestinal/imunologia , Linfócitos/imunologia , Macrófagos/imunologia , Modelos Teóricos , Técnicas de Cultura de Órgãos
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