Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Mucosal Immunol ; 10(5): 1133-1144, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28098246

RESUMO

IL-10 is a potent anti-inflammatory cytokine that inhibits the production of proinflammatory mediators. Signaling by IL-10 occurs through the IL-10 receptor (IL-10R), which is expressed in numerous cell types, including intestinal epithelial cells (IECs), where it is associated with development and maintenance of barrier function. Guided by an unbiased metabolomics screen, we identified tryptophan (Trp) metabolism as a major modifying pathway in interferon-γ (IFNγ)-dominant murine colitis. In parallel, we demonstrated that IFNγ induction of indoleamine 2,3-dioxygenase 1, an enzyme that catalyzes the conversion of Trp to kynurenine (Kyn), induces IL-10R1 expression. Based on these findings, we hypothesized that IL-10R1 expression on IEC is regulated by Trp metabolites. Analysis of the promoter region of IL-10R1 revealed a functional aryl hydrocarbon response element, which is induced by Kyn in luciferase-based IL-10R1 promoter assays. Additionally, this analysis confirmed that IL-10R1 protein levels were increased in response to Kyn in IEC in vitro. Studies using in vitro wounding assays revealed that Kyn accelerates IL-10-dependent wound closure. Finally, reduction of murine dextran sodium sulfate colitis through Kyn administration correlates with colonic IL-10R1 expression. Taken together, these results provide evidence on the importance of IL-10 signaling in intestinal epithelia and implicate AHR in the regulation of IL-10R1 expression in the colon.


Assuntos
Colite/imunologia , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Subunidade alfa de Receptor de Interleucina-10/metabolismo , Mucosa Intestinal/metabolismo , Triptofano/metabolismo , Animais , Sulfato de Dextrana , Modelos Animais de Doenças , Regulação da Expressão Gênica , Humanos , Interferon gama/metabolismo , Interleucina-10/metabolismo , Subunidade alfa de Receptor de Interleucina-10/genética , Cinurenina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Regiões Promotoras Genéticas/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais , Cicatrização
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...