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Am J Physiol Gastrointest Liver Physiol ; 303(2): G220-7, 2012 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-22595989

RESUMO

Intestinal epithelial cells (IEC) maintain gastrointestinal homeostasis by providing a physical and functional barrier between the intestinal lumen and underlying mucosal immune system. The activation of NF-κB and prevention of apoptosis in IEC are required to maintain the intestinal barrier and prevent colitis. How NF-κB activation in IEC prevents colitis is not fully understood. TNFα-induced protein 3 (TNFAIP3) is a NF-κB-induced gene that acts in a negative-feedback loop to inhibit NF-κB activation and also to inhibit apoptosis; therefore, we investigated whether TNFAIP3 expression in the intestinal epithelium impacts susceptibility of mice to colitis. Transgenic mice expressing TNFAIP3 in IEC (villin-TNFAIP3 Tg mice) were exposed to dextran sodium sulfate (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS), and the severity and characteristics of mucosal inflammation and barrier function were compared with wild-type mice. Villin-TNFAIP3 Tg mice were protected from DSS-induced colitis and displayed reduced production of NF-κB-dependent inflammatory cytokines. Villin-TNFAIP3 Tg mice were also protected from DSS-induced increases in intestinal permeability and induction of IEC death. Villin-TNFAIP3 Tg mice were not protected from colitis induced by TNBS. These results indicate that TNFAIP3 expression in IEC prevents colitis involving DSS-induced IEC death, but not colitis driven by T cell-mediated inflammation. As TNFAIP3 inhibits NF-κB activation and IEC death, expression of TNFAIP3 in IEC may provide an avenue to inhibit IEC NF-κB activation without inducing IEC death and inflammation.


Assuntos
Colite/metabolismo , Cisteína Endopeptidases/metabolismo , Sulfato de Dextrana/efeitos adversos , Mucosa Intestinal/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Ácido Trinitrobenzenossulfônico/toxicidade , Animais , Apoptose/efeitos dos fármacos , Colite/induzido quimicamente , Citocinas/biossíntese , Mucosa Intestinal/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , NF-kappa B/metabolismo , Índice de Gravidade de Doença , Proteína 3 Induzida por Fator de Necrose Tumoral alfa
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