Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.791
Filtrar
1.
Mol Immunol ; 119: 92-100, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32006824

RESUMO

Regulatory B10 cells have been shown to exhibit impaired functions in autoimmune diseases. However, the underlying mechanism is still obscure. In the present study, we aimed to understand the regulatory characteristics of regulatory B10 cells and how these cells are involved in the development of rheumatoid arthritis (RA). Here, we chose CD19+CD24hiCD27+ as the phenotype of regulatory B10 cells. We found that the frequencies of CD19+CD24hiCD27+ regulatory B10 cells were decreased and that their IL-10-producing function was impaired in patients with RA compared with healthy controls (HCs). The impairment in CD19+CD24hiCD27+ B10 cells was partially attributed to the decreased expression of CD27 induced by the upregulated CD70 expression on CD19 + B cells and CD4 + T cells. The proportion of CD19+CD24hiCD27+ regulatory B10 cells could be restored by blocking the CD70-CD27 interaction with an anti-CD70 antibody. Furthermore, the CD70-CD27 interaction significantly elevated IL-10 expression and might compensate for the decreased number of CD19+CD24hiCD27+ B cells. Hence, the CD70-CD27 interaction might play a critical role in the numerical and functional impairments of regulatory B10 cells, thus contributing to RA pathogenesis. In conclusion, the change in CD19+CD24hiCD27+ regulatory B10 cells in RA was only a consequence, not the cause, of RA development, but the increased expression of CD70 might be the culprit.


Assuntos
Artrite Reumatoide/imunologia , Linfócitos B Reguladores/imunologia , Ligante CD27/metabolismo , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/biossíntese , Adulto , Antígenos CD19 , Linfócitos B Reguladores/metabolismo , Antígeno CD24 , Regulação para Baixo , Feminino , Humanos , Interleucina-10/biossíntese , Interleucina-1beta/metabolismo , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/metabolismo
2.
Nat Commun ; 11(1): 252, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937752

RESUMO

Differentiation and homeostasis of Foxp3+ regulatory T (Treg) cells are strictly controlled by T-cell receptor (TCR) signals; however, molecular mechanisms that govern these processes are incompletely understood. Here we show that Bach2 is an important regulator of Treg cell differentiation and homeostasis downstream of TCR signaling. Bach2 prevents premature differentiation of fully suppressive effector Treg (eTreg) cells, limits IL-10 production and is required for the development of peripherally induced Treg (pTreg) cells in the gastrointestinal tract. Bach2 attenuates TCR signaling-induced IRF4-dependent Treg cell differentiation. Deletion of IRF4 promotes inducible Treg cell differentiation and rescues pTreg cell differentiation in the absence of Bach2. In turn, loss of Bach2 normalizes eTreg cell differentiation of IRF4-deficient Treg cells. Mechanistically, Bach2 counteracts the DNA-binding activity of IRF4 and limits chromatin accessibility, thereby attenuating IRF4-dependent transcription. Thus, Bach2 balances TCR signaling induced transcriptional activity of IRF4 to maintain homeostasis of thymically-derived and peripherally-derived Treg cells.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Animais , Fatores de Transcrição de Zíper de Leucina Básica/deficiência , Diferenciação Celular/imunologia , Cromatina/metabolismo , Colite/imunologia , Modelos Animais de Doenças , Epigênese Genética/imunologia , Fatores de Transcrição Forkhead/metabolismo , Trato Gastrointestinal/imunologia , Regulação da Expressão Gênica/imunologia , Homeostase/imunologia , Fatores Reguladores de Interferon/deficiência , Fatores Reguladores de Interferon/metabolismo , Interleucina-10/biossíntese , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Transdução de Sinais/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/metabolismo
3.
Arch Virol ; 165(3): 583-592, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31927635

RESUMO

Interferon lambda was discovered in recent years to be an antiviral agent, and research on different aspects of this antiviral factor in viral infection and investigations of its effectiveness are also progressing. The immunological effects of interferon lambda on different cell populations is not precisely known, which may be due to its use of a heterodimeric receptor consisting of IL-10R2 and IFN-λR1, which are not broadly expressed in all types of cells. In the present study, signaling by interferon lambda and its effect on the expression of hepatitis C virus (HCV) proteins were measured, and the expression pattern of some antiviral proteins and IL-10 levels were investigated in peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from 50 patients with chronic genotype 1a HCV infection and 10 healthy individuals as controls. The PBMCs were treated with various doses of interferon lambda at different times of cultivation. Real-time PCR was used for relative quantification of Mxa, PKR, OAS, ISG15 and HCV core mRNAs. Expression of the NS5A protein was measured by flow cytometry, and IL-10 production was assessed by ELISA. A significant increase in the expression of mRNA encoding antiviral proteins and a decrease in the expression of mRNAs encoding the HCV core protein were observed when cells were treated with interferon lambda in an intermittent manner. The expression of HCV NS5A protein and interleukin 10 levels were also lower than in the control group. It was shown that the maximum antiviral effect of interferon lambda in PBMCs is dependent on the dose and treatment time.


Assuntos
Hepatite C Crônica/imunologia , Interferons/farmacologia , Interleucinas/farmacologia , Leucócitos Mononucleares/imunologia , Proteínas do Core Viral/biossíntese , Proteínas não Estruturais Virais/biossíntese , Adulto , Antivirais/farmacologia , Linhagem Celular , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Interferon-alfa/imunologia , Interferon-alfa/farmacologia , Interferons/imunologia , Interleucina-10/biossíntese , Interleucinas/imunologia , Leucócitos Mononucleares/metabolismo , Pessoa de Meia-Idade , RNA Mensageiro/biossíntese , RNA Viral/biossíntese , Proteínas do Core Viral/genética
4.
Clin Exp Rheumatol ; 37 Suppl 119(4): 76-81, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31587692

RESUMO

OBJECTIVES: Vitamin D status influences the risk to develop autoimmune diseases affecting the percentage and/or functions of regulatory T cells (Tregs). Since low levels of 25 (OH) D have been decreased in patients with systemic sclerosis (SSc), we aimed to study the effect of Vitamin D3 (cholecalciferol) supplementation on Tregs frequencies and functions. METHODS: Peripheral blood and sera samples were obtained from 45 SSc patients and controls (HC). A number of eighteen SSc patients had consumed Cholecalciferol (orally) at the dose of 25.000 UI/month for 6 months at the time of enrollment. 25(OH)D serum levels were measured and VDR polymorphisms, were genotyped by polymerase chain reaction (PCR). Tregs isolated from peripheral blood mononuclear cells were in vitro expanded and a suppression assay was performed. Flow cytometry analysis was then carried out. Finally, IL-10 production was assayed by ELISA. RESULTS: Low serum levels of 25(OH)D were detected in SSc patients. The percentage of Tregs in SSc patients was similar to controls, but, among SSc patients, it was higher in those patients taking cholecalciferol. Tregs capability to suppress T cell proliferation was impaired in SSc patients and not restored after in vitro pre-treatment with the active form of Vitamin D (1,25(OH)2D3); but at the same time the production of IL-10 was increased in treated samples obtained from patients. The lack of response of Tregs from SSc patients to 1,25(OH)2D3 treatment in vitro was not due to altered Vitamin D/VDR signalling. CONCLUSIONS: Altogether, our results indicate that the increased production of IL-10 by 1,25(OH)2D3 -treated Tregs could provide a "suppressive" cytokine milieu able to modulate immune response but it is not sufficient to restore the immune suppressive functions of Tregs.


Assuntos
Interleucina-10/biossíntese , Escleroderma Sistêmico , Linfócitos T Reguladores/efeitos dos fármacos , Vitamina D , Estudos de Casos e Controles , Suplementos Nutricionais , Feminino , Humanos , Leucócitos Mononucleares , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/metabolismo , Vitamina D/farmacologia
5.
Life Sci ; 235: 116838, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31493482

RESUMO

AIMS: This work aimed to evaluate the regulatory function of IL-10-producing B cells in viral myocarditis (VMC). MAIN METHODS: We adoptively transferred purified IL-10-producing B cells to VMC mice via the tail vein. We observed the inflammatory responses and cardiac lesions by histological analysis, examined the proportions of spleen Th1 and T17 cells by flow cytometry and expression levels of related transcription factors (T-bet and RORγt) by reverse transcription polymerase chain reaction (RT-PCR), and calculated the cardiac pathological scores and the mean survival times. KEY FINDINGS: IL-10-producing B cells were found to be T cell-dependent in the pathogenesis of VMC. They mainly downregulated T-bet and RORγt mRNA levels to decrease the proportions of Th1 and Th17 cells, thereby restraining the inflammation and damage in the myocardium in B cell-deficient VMC mice. Adoptive transfer of IL-10-producing B cells before VMC induction also normalized the inflammatory responses and prolonged the survival time in wild-type (WT) VMC mice. While the transfer of IL-10-producing B cells on day 3 of VMC alleviated the severity of disease, it did not extend the mean survival time of VMC mice. By contrast, IL-10-producing B cells showed no effect on day 7 of VMC. In conclusion, IL-10-producing B cells downregulate the proportion of Th1 and Th17 cells to alleviate inflammatory damage in the myocardium during VMC before the induction or the early phase of disease. SIGNIFICANCE: These findings suggest that IL-10-producing B cells may be a new therapeutic target for modulating the immune response in VMC.


Assuntos
Linfócitos B/metabolismo , Enterovirus Humano B/imunologia , Inflamação/fisiopatologia , Interleucina-10/fisiologia , Miocardite/fisiopatologia , Células Th1/imunologia , Células Th17/imunologia , Transferência Adotiva , Animais , Infecções por Coxsackievirus/imunologia , Infecções por Coxsackievirus/virologia , Regulação para Baixo , Interleucina-10/biossíntese , Masculino , Camundongos , Miocardite/metabolismo , Miocardite/patologia , Miocardite/virologia , Miocárdio/patologia , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/biossíntese , Taxa de Sobrevida , Proteínas com Domínio T/biossíntese
6.
Artigo em Inglês | MEDLINE | ID: mdl-31119102

RESUMO

Cutaneous leishmaniasis (CL) caused by infection with Leishmania braziliensis is characterized by an exaggerated inflammatory response that controls the parasite burden, but also contributes to pathology. While myeloid cells are required to eliminate the parasite, recent studies indicate that they may also participate in the inflammatory response driving disease progression. The innate immune response to leishmania is driven in part by the Toll-like receptors (TLRs) TLR2, TLR4, and TLR9. In this study, we used flow cytometric analysis to compare TLR2 and TLR4 expression in monocyte subsets (classical, intermediate, and non-classical) from CL patients and healthy subjects (HS). We also determined if there was an association of either the pro-inflammatory cytokine TNF or the anti-inflammatory cytokine IL-10 with TLR2 or TLR4 expression levels after L. braziliensis infection. In vitro infection with L. braziliensis caused CL monocytes to up-regulate TLR2 and TLR4 expression. We also found that intermediate monocytes expressed the highest levels of TLR2 and TLR4 and that infected monocytes produced more TNF and IL-10 than uninfected monocytes. Finally, while classical and intermediate monocytes were mainly responsible for TNF production, classical monocytes were the main source of IL-10. Collectively, our studies revealed that up-regulated TLR2/4 expression and TNF production by intermediate/inflammatory subsets of monocytes from patients correlates with detrimental outcome of cutaneous leishmaniasis.


Assuntos
Interleucina-10/biossíntese , Leishmania braziliensis/imunologia , Leishmaniose Cutânea/patologia , Monócitos/imunologia , Receptor 2 Toll-Like/biossíntese , Receptor 4 Toll-Like/biossíntese , Fator de Necrose Tumoral alfa/biossíntese , Adulto , Células Cultivadas , Feminino , Expressão Gênica , Humanos , Leishmaniose Cutânea/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/parasitologia , Adulto Jovem
7.
Infect Immun ; 87(8)2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31085707

RESUMO

The major problem with Chagas disease is evolution of the chronic indeterminate form to a progressive cardiac disease. Treatment diminishes parasitemia but not clinical progression, and the immunological features involved are unclear. Here, we studied the clinical course and the immune response in patients with chronic-phase Chagas disease at 48 months after benznidazole treatment. Progression to the cardiac form of Chagas disease or its aggravation was associated with higher in vitro antigen-specific production of interferon gamma (IFN-γ) in patients with cardiac Chagas disease than in patients with the indeterminate form. Predominance of IFN-γ production over interleukin-10 (IL-10) production in antigen-specific cultures was associated with cardiac involvement. Significantly higher numbers of antigen-specific T helper 1 cells (T-Bet+ IFN-γ+) and a significantly higher IFN-γ+/IL-10+ ratio were observed in patients with cardiac Chagas disease than in patients with the indeterminate form. Cardiac damage was associated with higher numbers of T helper cells than cytotoxic T lymphocytes producing IFN-γ. Patients with cardiac Chagas disease had predominant CD25- and CD25low T regulatory (Treg) subpopulations, whereas patients with the indeterminate form manifested a higher relative mean percentage of CD25high Treg subpopulations. These findings suggest that at 48 months after benznidazole treatment, the disease can worsen or progress to the cardiac form. The progression may be related to increased IFN-γ production (mostly from CD4+ T cells) relative to IL-10 production and increased Treg percentages. Patients with the indeterminate form of Chagas disease show a more balanced ratio of proinflammatory and anti-inflammatory cytokines.


Assuntos
Doença de Chagas/tratamento farmacológico , Citocinas/biossíntese , Nitroimidazóis/uso terapêutico , Linfócitos T/imunologia , Idoso , Doença de Chagas/imunologia , Feminino , Humanos , Imunofenotipagem , Interferon gama/biossíntese , Interleucina-10/biossíntese , Masculino , Pessoa de Meia-Idade , Linfócitos T Reguladores/imunologia
8.
Colloids Surf B Biointerfaces ; 181: 125-133, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31128512

RESUMO

One of the events occurring when a biomaterial is implanted in an host is the protein deposition onto its surface, which might regulate cell responses. When a biomaterial displays a compromised biocompatibility, distinct complement pathways can be activated to produce a foreign body reaction. In this article, we have designed different types of biomaterial surfaces to study the inflammation process. Here, we used different concentrations of (3-glycidoxypropyl)-trimethoxysilane (GPTMS), an organically-modified alkoxysilane as a precursor for the synthesis of various types of sol-gel materials functionalizing coatings for titanium implants to regulate biological responses. Our results showed that greater GPTMS surface concentrations induced greater secretion of TNF-α and IL-10 on RAW 264.7 macrophages. When implanted into rabbit tibia, osseointegration decreased with higher GPTMS concentrations. Interestingly, higher deposition of complement-related proteins C-reactive protein (CRP) and ficolin-2 (FCN2), two main activators of distinct complement pathways, was observed. Taking all together, inflammatory potential increase seems to be GPTMS concentration-dependent. Our results show that a greater adsorption of complement proteins can condition macrophage polarization.


Assuntos
Materiais Biocompatíveis/farmacologia , Proteínas do Sistema Complemento/metabolismo , Macrófagos/efeitos dos fármacos , Silanos/farmacologia , Titânio/farmacologia , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Interleucina-10/biossíntese , Macrófagos/metabolismo , Camundongos , Tamanho da Partícula , Células RAW 264.7 , Coelhos , Silanos/síntese química , Silanos/química , Propriedades de Superfície , Tíbia/efeitos dos fármacos , Tíbia/metabolismo , Titânio/química , Fator de Necrose Tumoral alfa/biossíntese
9.
Biosci Biotechnol Biochem ; 83(7): 1343-1353, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31038020

RESUMO

We previously reported that the major component of Enterococcus faecalis strain EC-12 (EC-12) inducing production of Interleukin (IL)-12 in mouse/human immune cells was its own RNA. This study aimed to investigate if RNase A-treated EC-12 could also produce IL-10 and to evaluate the possible effects of IL-10 produced by RNase A-treated EC-12. Three experiments were conducted: (1) Assessment of the effect of RNase A-treated EC-12 on transcriptome profiles and biological pathways in human peripheral blood mononuclear cells; (2) Determination of cytokine concentration in its culture supernatants; and (3) Supplementation of RNase A-treated EC-12 (RN) to mice with dextran sodium sulfate-induced colitis. Treatment of EC-12 with RNase A inhibited inflammatory response including the potency to induce IL-12 production, while it did not affect IL-10 production (Experiment 1 and 2). Colitis symptoms were milder in RN than in PBS-supplemented controls (Experiment 3). RNase A-treated EC-12 likely became an anti-inflammatory agent primarily inducing IL-10 production.


Assuntos
Anti-Inflamatórios/farmacologia , Enterococcus faecalis/efeitos dos fármacos , Ribonuclease Pancreático/farmacologia , Animais , Meios de Cultura , Sulfato de Dextrana/efeitos adversos , Humanos , Interleucina-10/biossíntese , Camundongos
10.
Chem Biol Interact ; 306: 110-116, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30991045

RESUMO

MicroRNAs (miRNAs) have been implicated in both biological and pathological processes in patients with systemic lupus erythematosus (SLE). Previous studies have demonstrated dysregulated expression of miR-199-3p, interleukin (IL)-10, and poly (ADP-ribose) polymerase-1 (PARP-1) in SLE. However, the underlying mechanisms of these aberrations have not been fully elucidated. In this study, we investigated the mechanism through which miR-199-3p dysregulation contributed to the pathogenesis of SLE. Altered gene expression was assessed by ChIP analysis. We then silenced the expression of candidate genes using siRNA for functional analysis; mRNA expression, protein levels, and protein expression were determined by qRT-PCR, ELISA, and western blotting, respectively. According to ChIP and qRT-PCR results, miR-199-3p was up-regulated in SLE patients. Moreover, IL-10 was found to be highly expressed in SLE patients by ELISA. Further, PARP1 was significantly down-regulated in SLE patients based on western blotting. Our results also indicated that miR-199-3p inhibits PARP1 expression by activating the ERK1/2 pathway, thereby increasing IL-10 expression. Significantly up-regulated miR-199-3p was inversely related to PARP-1 expression and positively correlated with IL-10 levels in SLE. As miR-199-3p was shown to target PARP-1 to activate the ERK1/2 pathway and promote IL-10 production, restoring physiological miR-199-3p levels could represent a potential therapeutic strategy for SLE treatment.


Assuntos
Interleucina-10/biossíntese , Lúpus Eritematoso Sistêmico/metabolismo , MicroRNAs/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Adulto , Feminino , Células HEK293 , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/genética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
11.
Pharm Biol ; 57(1): 161-168, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30905278

RESUMO

CONTEXT: ß-Sitosterol (BS), the primary constituent of plants and vegetables, exhibits multiple biological effects. OBJECTIVE: This study explores its effect of immune-regulation on macrophages and its potential for rheumatoid arthritis (RA) therapy. MATERIALS AND METHODS: In vitro, bone marrow-derived macrophages (BMDMs) were treated with 5, 25 and 50 µM BS in the M1 or M2 polarization conditions. In vivo, either i.p. injection with 20 or 50 mg/kg BS every 2 d after boost immunization of collagen-induced arthritis (CIA) or adoptive transfer of 2 × 106 BS-treated BMDMs (BS-BMDMs) at the day before CIA were adopted in mice to test the therapeutic effect. IL-10 antibody depletion was used in the period of above treatments to discuss the underlying mechanism. RESULTS: The phenotypes and function of BMDMs showed that 5, 25 and 50 µM BS significantly repressed the M1 polarization and augmented M2 polarization dependent upon concentration. The expression of iNOS, IL-1ß, CD86 and MHCII in 25 µM BS-treated M1-polarized BMDMs was reduced by 50.2, 47.1, 87.1 and 31.3%, respectively. In contrast, the expression of arginase-1, IL-10, CD163 and CD206 in 25 µM BS-treated M2-polarized BMDMs was increased by 65.6, 107.4, 23.5 and 51.3%, respectively. In CIA mice, either i.p. injection with BS or adoptive transfer of BS-BMDMs could alleviate the symptoms of ankle swelling (vehicle group: 3.13 ± 0.102 mm; 20 mg/kg BS group: 2.64 ± 0.043 mm; 50 mg/kg BS group: 2.36 ± 0.084 mm; BMDMs group: 3.09 ± 0.174 mm; BS-BMDMs group: 2.43 ± 0.042 mm), reduce the levels of collagen-specific antibodies (IgG and IgG1, but not IgG2c, p < 0.05) and inhibit the production of pro-inflammatory cytokines (p < 0.05). Depletion of IL-10 counteracted the effect of BS treatment (α-IL-10 vs. RatIgG1, p < 0.01 on day 16), highlighting the role of IL-10 in the anti-inflammatory response. CONCLUSIONS: These results suggested that BS could modulate the functions of macrophages and might be a promising agent for RA therapy.


Assuntos
Artrite Experimental/tratamento farmacológico , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Sitosteroides/farmacologia , Animais , Artrite Experimental/imunologia , Polaridade Celular/efeitos dos fármacos , Polaridade Celular/imunologia , Citocinas/biossíntese , Citocinas/sangue , Citocinas/imunologia , Relação Dose-Resposta a Droga , Interleucina-10/biossíntese , Interleucina-10/imunologia , Ativação de Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
12.
Nat Immunol ; 20(4): 471-481, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30778241

RESUMO

Foxp3+ regulatory T cells (Treg cells) are crucial for the maintenance of immune homeostasis both in lymphoid tissues and in non-lymphoid tissues. Here we demonstrate that the ability of intestinal Treg cells to constrain microbiota-dependent interleukin (IL)-17-producing helper T cell (TH17 cell) and immunoglobulin A responses critically required expression of the transcription factor c-Maf. The terminal differentiation and function of several intestinal Treg cell populations, including RORγt+ Treg cells and follicular regulatory T cells, were c-Maf dependent. c-Maf controlled Treg cell-derived IL-10 production and prevented excessive signaling via the kinases PI(3)K (phosphatidylinositol-3-OH kinase) and Akt and the metabolic checkpoint kinase complex mTORC1 (mammalian target of rapamycin) and expression of inflammatory cytokines in intestinal Treg cells. c-Maf deficiency in Treg cells led to profound dysbiosis of the intestinal microbiota, which when transferred to germ-free mice was sufficient to induce exacerbated intestinal TH17 responses, even in a c-Maf-competent environment. Thus, c-Maf acts to preserve the identity and function of intestinal Treg cells, which is essential for the establishment of host-microbe symbiosis.


Assuntos
Imunoglobulina A/biossíntese , Intestinos/imunologia , Microbiota , Proteínas Proto-Oncogênicas c-maf/fisiologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Animais , Células Cultivadas , Colite/imunologia , Citocinas/metabolismo , Disbiose , Regulação da Expressão Gênica , Homeostase , Interleucina-10/biossíntese , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-maf/genética , Proteínas Proto-Oncogênicas c-maf/metabolismo , Linfócitos T Reguladores/enzimologia
13.
Acta Ophthalmol ; 97(5): e780-e784, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30761764

RESUMO

PURPOSE: Evidence exists that the interleukin (IL)-10 family of cytokines is involved in autoimmune diseases. The aim of this study was to analyse the levels of the IL-10 family cytokines IL-10, IL-19, IL-20, IL-22, IL-26, IL-28A and IL-29 in aqueous humour (AH) samples from patients with specific uveitic entities. In addition, we correlated their levels with the levels of the proinflammatory cytokines tumour necrosis factor-α (TNF-α) and IL-1ß. METHODS: Aqueous humour (AH) samples from patients with active uveitis associated with Behçet's disease (BD; n = 13), sarcoidosis (n = 8), human leucocyte antigen (HLA)-B27-related inflammation (n = 12), Vogt-Koyanagi-Harada (VKH) disease (n = 12) and control subjects (n = 9) were assayed with the use of a multiplex assay. RESULTS: Of all the IL-10 family cytokines studied, only IL-19 levels were significantly higher in AH samples of patients (n = 45) than in controls (p = 0.022). When comparing the four individual disease groups to controls, IL-19 levels were only significantly higher in HLA-B27-associated uveitis (p < 0.001). IL-19 levels were significantly higher in patients with HLA-B27-associated uveitis than in patients with BD, sarcoidosis and VKH disease (p < 0.001; p = 0.002; p < 0.001, respectively). Significant correlations were found between AH levels of IL-19 and AH levels of TNF-α, (r = 0.3; p = 0.03) and IL-1ß (r = 0.56; p < 0.001). CONCLUSIONS: Among the IL-10 family cytokines analysed, IL-19 demonstrated the highest expression in endogenous uveitis, particularly in HLA-B27-associated uveitis. IL-19 thus might assist in the regulation of inflammation in HLA-B27-associated uveitis.


Assuntos
Humor Aquoso/metabolismo , Autoimunidade , Antígeno HLA-B27/imunologia , Interleucina-10/biossíntese , Interleucinas/metabolismo , Uveíte/metabolismo , Humor Aquoso/imunologia , Biomarcadores/metabolismo , Angiofluoresceinografia , Fundo de Olho , Humanos , Oftalmoscopia , Índice de Gravidade de Doença , Microscopia com Lâmpada de Fenda , Uveíte/diagnóstico , Uveíte/imunologia
14.
Biochem Biophys Res Commun ; 510(3): 435-441, 2019 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-30722992

RESUMO

Inflammatory bowel disease (IBD) has been well-documented as a chronic gastrointestinal autoimmune disease, but its etiology remains to be elusive. Ascl2 (achaete-scute complex homologue 2), identified as a homologue of the Drosophila achaete-scute gene, has been shown to play an essential for the pathogenesis of autoimmune diseases and cancers. However, whether it is associated with the pathogenesis of IBD remains unclear. Here, we demonstrated that Ascl2 was greatly down-regulated in human IBD and experimental colitis. Interestingly, CD4+ T cell expression of Ascl2 was regulated by intestinal microbiota. Moreover, we revealed that Ascl2 inhibited the differentiation of Th17 cells and restrained their pathogenicity through facilitating IL-10 production. We further showed that Blimp-1 might be involved in the Ascl2-inducing IL-10 expression in CD4+ T cells under Th17 differentiating condition. Notably, lentivirus-mediated overexpression of Ascl2 remarkably alleviated the severity of 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-induced colitis in mice, with decreased level of colonic IL-17A. Our findings demonstrated an unappreciated mechanism whereby Ascl2 negatively modulates pathogenic Th17 cell differentiation via promoting IL-10 production, and alleviates intestinal inflammation. Thus, Ascl2 may serve as a novel therapeutic target of IBD.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Doenças Inflamatórias Intestinais/imunologia , Interleucina-10/biossíntese , Células Th17/imunologia , Animais , Linfócitos T CD4-Positivos/metabolismo , Diferenciação Celular , Colite/induzido quimicamente , Colite/imunologia , Microbioma Gastrointestinal , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Camundongos , Fator 1 de Ligação ao Domínio I Regulador Positivo/metabolismo , Células Th17/metabolismo
15.
Inflammation ; 42(3): 987-993, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30707387

RESUMO

Umbilical cord blood mesenchymal stem cells (UCB-MSCs) have been shown to be a source of stem cells for use in cellular therapies and have immunomodulatory effects on several immune cells in an inflammatory environment. However, whether UCB-MSCs have immunomodulatory effects against lipopolysaccharide (LPS)-induced inflammatory cytokine secretion in macrophages and whether it is involved in phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway remain unclear. After co-culture of UCB-MSCs and phorbol 12-myristate 13-acetate (PMA)-activated human THP-1 cells using a transwell system, it showed that LPS significantly induced increases in the expression levels of interleukin 10 (IL-10), interleukin 37 (IL-37), phospho-PI3K (p-PI3K), and phospho-Akt (p-Akt) in macrophages. UCB-MSCs upregulated the expression of IL-10, IL-37, p-PI3K, and p-Akt, while it had no obvious effect on PI3K and Akt levels. Inhibitors of PI3K (LY294002) significantly suppressed the expression of IL-10, IL-37, p-PI3K, and p-Akt; however, it had no effect on the expression levels of PI3K and Akt. The present study demonstrated that UCB-MSCs increased the LPS-stimulated expression of IL-10 and IL-37 in macrophages through the PI3K/Akt signaling pathway.


Assuntos
Interleucina-10/biossíntese , Interleucina-1/biossíntese , Macrófagos/metabolismo , Células-Tronco Mesenquimais/fisiologia , Técnicas de Cocultura , Sangue Fetal/citologia , Humanos , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células THP-1/citologia , Células THP-1/metabolismo
16.
J Neuroinflammation ; 16(1): 2, 2019 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-30611291

RESUMO

BACKGROUND: Traumatic brain injury (TBI) is a major cause for long-term disability, yet the treatments available that improve outcomes after TBI limited. Neuroinflammatory responses are key contributors to determining patient outcomes after TBI. Transplantation of mesenchymal stem cells (MSCs), which release trophic and pro-repair cytokines, represents an effective strategy to reduce inflammation after TBI. One such pro-repair cytokine is interleukin-10 (IL-10), which reduces pro-inflammatory markers and trigger alternative inflammatory markers, such as CD163. In this study, we tested the therapeutic effects of MSCs that were engineered to overexpress IL-10 when transplanted into rats following TBI in the medial frontal cortex. METHODS: Thirty-six hours following TBI, rats were transplanted with MSCs and then assessed for 3 weeks on a battery of behavioral tests that measured motor and cognitive abilities. Histological evaluation was then done to measure the activation of the inflammatory response. Additionally, immunomodulatory effects were evaluated by immunohistochemistry and Western blot analyses. RESULTS: A significant improvement in fine motor function was observed in rats that received transplants of MSCs engineered to overexpress IL-10 (MSCs + IL-10) or MSCs alone compared to TBI + vehicle-treated rats. Although tissue spared was unchanged, anti-inflammatory effects were revealed by a reduction in the number of glial fibrillary acidic protein cells and CD86 cells in both TBI + MSCs + IL-10 and TBI + MSC groups compared to TBI + vehicle rats. Microglial activation was significantly increased in the TBI + MSC group when compared to the sham + vehicle group. Western blot data suggested a reduction in tumor necrosis factor-alpha in the TBI + MSCs + IL-10 group compared to TBI + MSC group. Immunomodulatory effects were demonstrated by a shift from classical inflammation expression (CD86) to an alternative inflammation state (CD163) in both treatments with MSCs and MSCs + IL-10. Furthermore, co-labeling of both CD86 and CD163 was detected in the same cells, suggesting a temporal change in macrophage expression. CONCLUSIONS: Overall, our findings suggest that transplantation of MSCs that were engineered to overexpress IL-10 can improve functional outcomes by providing a beneficial perilesion environment. This improvement may be explained by the shifting of macrophage expression to a more pro-repair state, thereby providing a possible new therapy for treating TBI.


Assuntos
Encefalite/cirurgia , Interleucina-10/biossíntese , Interleucina-10/uso terapêutico , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Lesões Encefálicas Traumáticas/complicações , Modelos Animais de Doenças , Encefalite/etiologia , Engenharia Genética/métodos , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Interleucina-10/genética , Locomoção/fisiologia , Masculino , Aprendizagem em Labirinto/fisiologia , Ratos , Ratos Sprague-Dawley , Transdução Genética
17.
Cytotherapy ; 21(2): 148-161, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30595353

RESUMO

Bone marrow-derived stromal cells or mesenchymal stromal cells (BMSCs or MSCs, as we will call them in this work) are multipotent progenitor cells that can differentiate into osteoblasts, adipocytes and chondrocytes. In addition, MSCs have been shown to modulate the function of a variety of immune cells. Donor age has been shown to affect the regenerative potential, differentiation, proliferation and anti-inflammatory potency of MSCs; however, the impact of donor age on their immunosuppressive activity is unknown. In this study, we evaluated the ability of MSCs derived from very young children and adults on T-cell suppression and cytokine secretion by monocytes/macrophages. MSCs were obtained from extra digits of children between 10 and 21 months and adults between 28 and 64 years of age. We studied cell surface marker expression, doubling time, lineage differentiation potential and immunosuppressive function of the MSCs. Young MSCs double more quickly and differentiate into bone and fat cells more efficiently than those from older donors. They also form more and dense colonies of fibroblasts (colony forming unit-fibroblast [CFU-F]). MSCs from both young and adult subjects suppressed T-cell proliferation in a mitogen-induced assay at 1:3 and 1:30 ratios. At a 1:30 ratio, however, MSCs from adults did not, but MSCs from infants did suppress T-cell proliferation. In the mixed lymphocyte reaction assay, MSCs from infants produced similar levels of suppression at all three MSC/T-cell ratios, but adult MSCs only inhibited T-cell proliferation at a 1:3 ratio. Cytokine analyses of co-cultures of MSCs and macrophages showed that both adult and young MSCs suppress tumor necrosis factor alpha (TNF-α) and induce interleukin-10 (IL-10) production in macrophage co-culture assay in a similar manner. Overall, this work shows that developing MSCs display a higher level of immunosuppression than mature MSCs.


Assuntos
Interleucina-10/biossíntese , Células-Tronco Mesenquimais/imunologia , Polidactilia/cirurgia , Fator de Necrose Tumoral alfa/biossíntese , Adulto , Fatores Etários , Diferenciação Celular/imunologia , Proliferação de Células , Células Cultivadas , Técnicas de Cocultura , Células do Tecido Conjuntivo/fisiologia , Feminino , Humanos , Lactente , Teste de Cultura Mista de Linfócitos , Masculino , Pessoa de Meia-Idade , Polidactilia/patologia
18.
Curr Microbiol ; 76(1): 29-36, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30302554

RESUMO

Lactic acid bacteria are the majority fermentation starter in the traditional fermented foods. In this research, a promising Lactobacillus plantarum was isolated from Sichuan pickle and its adhesion properties were analyzed in simulated gastrointestinal fluid with different methods. Meanwhile, the immunomodulatory effect of this strain was also evaluated in the Caco-2 cells. Results found that adhesion-related mub genes and other genes like lsp and tuf were upregulated in different culture times. Furthermore, L. plantarum cultured at alkaline environment revealed some anti-inflammation activity through inhibited expression of cytokine IL-8 and increased expression of anti-inflammatory cytokine IL-10 in Caco-2 cells. The texture of yogurt after fermented by this kind of isolated strain was also investigated, which provides the foundation for the further development and application of this kind of strain in food production. More investigations need to be carried out to determine whether this probiotic contributes to regulation of intestinal flora and prevention of gut inflammation.


Assuntos
Aderência Bacteriana/genética , Cucumis sativus/microbiologia , Lactobacillus plantarum/imunologia , Lactobacillus plantarum/metabolismo , Células CACO-2 , Linhagem Celular Tumoral , Fermentação , Humanos , Interleucina-10/biossíntese , Interleucina-8/biossíntese , Microscopia Eletrônica de Varredura , Probióticos/farmacologia , Iogurte/microbiologia
20.
J Clin Neurosci ; 62: 121-127, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30579843

RESUMO

The present study evaluated the diagnostic and predictive potential of microRNA-93 in acute ischemic stroke (AIS) patients within 6 h of stroke onset and its regulation on microglial inflammation in vitro. Our results showed that the miR-93 levels in plasma and neutrophil detected by real-time PCR were evidently reduced in AIS patients, and Pearson's correlation analysis showed that miR-93 levels in plasma and neutrophils had a significant positive linear correlation. Moreover, miR-93 levels in plasma and neutrophils of stroke patients at time of admission were not correlated with infarct volume and NIHSS (National Institute of Health stroke scale) scores at admission, but neutrophil miR-93 levels were positively correlated with the Barthel Index 7 days after stroke. Importantly, miR-93 levels in plasma and neutrophil of AIS patients were negatively correlated with the expression of TNF-α and IL-10. Furthermore, in vitro treatment with miR-93 agomir decreased the OGD (Oxygen and glucose deprivation)-induced proliferation of BV2 microglial cells tested by Flow cytometry. We demonstrated that miR-93 in blood has a potential to facilitate the diagnosis and prediction of neurological outcomes of acute ischemic stroke, and is involved in inflammation possibly through targeting the proliferation of microglia.


Assuntos
MicroRNAs/sangue , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/diagnóstico , Biomarcadores/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/diagnóstico , Feminino , Humanos , Inflamação/metabolismo , Interleucina-10/biossíntese , Masculino , MicroRNAs/análise , Microglia/metabolismo , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Acidente Vascular Cerebral/sangue
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA