Expression of TNFAIP3 in intestinal epithelial cells protects from DSS- but not TNBS-induced colitis.
Am J Physiol Gastrointest Liver Physiol
; 303(2): G220-7, 2012 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-22595989
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ácido Trinitrobenzenossulfônico
/
Cisteína Endopeptidases
/
Sulfato de Dextrana
/
Colite
/
Peptídeos e Proteínas de Sinalização Intracelular
/
Mucosa Intestinal
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article