Expression of TNFAIP3 in intestinal epithelial cells protects from DSS- but not TNBS-induced colitis

Lesley Rhee, Stephen F. Murphy, Lauren E. Kolodziej, Wesley A. Grimm, Christopher R. Weber, James P. Lodolce, Jonathan E. Chang, Sarah J. Bartulis, Jeannette S. Messer, Jeff R. Schneider, Shirley Paski, Thomas M. Nero, David L. Boone

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)G220-G227
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume303
Issue number2
DOIs
StatePublished - Jul 15 2012

Keywords

  • A20
  • Apoptosis
  • Inflammation
  • NF-κB

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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