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 ; 9(5): 1250-62, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26838049

RESUMO

Inflammatory bowel disease (IBD) is associated with dysregulated macrophage responses, such that quiescent macrophages acquire a pro-inflammatory activation state and contribute to chronic intestinal inflammation. The transcriptional events governing macrophage activation and gene expression in the context of chronic inflammation such as IBD remain incompletely understood. Here, we identify Kruppel-like transcription factor-6 (KLF6) as a critical regulator of pathogenic myeloid cell activation in human and experimental IBD. We found that KLF6 was significantly upregulated in myeloid cells and intestinal tissue from IBD patients and experimental models of IBD, particularly in actively inflamed regions of the colon. Using complementary gain- and loss-of-function studies, we observed that KLF6 promotes pro-inflammatory gene expression through enhancement of nuclear factor κB (NFκB) signaling, while simultaneously suppressing anti-inflammatory gene expression through repression of signal transducer and activator of transcription 3 (STAT3) signaling. To study the in vivo role of myeloid KLF6, we treated myeloid-specific KLF6-knockout mice (Mac-KLF6-KO) with dextran sulfate sodium (DSS) and found that Mac-KLF6-KO mice were protected against chemically-induced colitis; this highlights the central role of myeloid KLF6 in promoting intestinal inflammation. Collectively, our results point to a novel gene regulatory program underlying pathogenic, pro-inflammatory macrophage activation in the setting of chronic intestinal inflammation.


Assuntos
Colite Ulcerativa/imunologia , Colite/imunologia , Colo/imunologia , Doença de Crohn/imunologia , Fatores de Transcrição Kruppel-Like/imunologia , Macrófagos/imunologia , Proteínas Proto-Oncogênicas/imunologia , Animais , Linhagem Celular , Plasticidade Celular/imunologia , Colite/induzido quimicamente , Colite/genética , Colite/patologia , Colite Ulcerativa/genética , Colite Ulcerativa/patologia , Colo/patologia , Doença de Crohn/genética , Doença de Crohn/patologia , Sulfato de Dextrana , Regulação da Expressão Gênica , Humanos , Fator 6 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/deficiência , Fatores de Transcrição Kruppel-Like/genética , Ativação de Macrófagos , Macrófagos/patologia , Masculino , Camundongos , Camundongos Knockout , Monócitos/imunologia , Monócitos/patologia , NF-kappa B/genética , NF-kappa B/imunologia , Proteínas Proto-Oncogênicas/deficiência , Proteínas Proto-Oncogênicas/genética , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/imunologia , Transdução de Sinais , Transcrição Gênica
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...