| First Author | Rhee L | Year | 2012 |
| Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 303 |
| Issue | 2 | Pages | G220-7 |
| PubMed ID | 22595989 | Mgi Jnum | J:191362 |
| Mgi Id | MGI:5461599 | Doi | 10.1152/ajpgi.00077.2012 |
| Citation | Rhee L, et al. (2012) 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 |
| abstractText | 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-kappaB and prevention of apoptosis in IEC are required to maintain the intestinal barrier and prevent colitis. How NF-kappaB activation in IEC prevents colitis is not fully understood. TNFalpha-induced protein 3 (TNFAIP3) is a NF-kappaB-induced gene that acts in a negative-feedback loop to inhibit NF-kappaB 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-kappaB-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-kappaB activation and IEC death, expression of TNFAIP3 in IEC may provide an avenue to inhibit IEC NF-kappaB activation without inducing IEC death and inflammation. |
