Peroxisome proliferator activated receptor γ in colonic epithelial cells protects against experimental inflammatory bowel disease

M. Adachi, R. Kurotani, K. Morimura, Y. Shah, M. Sanford, B. B. Madison, D. L. Gumucio, H. E. Marin, J. M. Peters, H. A. Young, F. J. Gonzalez

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Abstract

Introduction: Peroxisome proliferator activated receptor γ (PPARγ) is expressed in epithelial cells, macrophage, and T and B lymphocytes. Ligand induced activation of PPARγ was reported to attenuate colitis activity but it is not clear whether this protection is mediated by epithelial or leucocyte PPARγ. Methods: Mice with targeted disruption of the PPARγ gene in intestinal epithelial cells, generated using a villin-Cre transgene and floxed PPARγ allele and designated PPARγΔIEpC, were compared with littermate mice having only the PPARγ floxed allele with no Cre transgene that expressed PPARγ in the gut, designated PPARγF/F. Colitis was induced by administering dextran sodium sulphate (DSS) and the two mouse lines compared for typical symptoms of disease and expression of inflammatory cytokines. Results: PPARγΔIEpC mice displayed reduced expression of the PPARγ target genes ADRP and FABP in the gut but were otherwise normal. Increased susceptibility to DSS induced colitis, as defined by body weight loss, colon length, diarrhoea, bleeding score, and altered histology, was found in PPARγΔIEpC mice in comparison with PPARγF/F mice. Interleukin (IL)-6, IL-1β, and tumour necrosis factor α mRNA levels in colons of PPARγ ΔIEpC mice treated with DSS were higher than in similarly treated PPARγF/F mice. The PPARγ ligand rosiglitazone decreased the severity of DSS induced colitis and suppressed cytokine production in both PPARγF/F and PPARγΔIEpC mice. Conclusions: These studies reveal that PPARγ expressed in the colonic epithelium has an endogenous role in protection against DSS induced colitis and that rosiglitazone may act through a PPARγ independent pathway to suppress inflammation.

Original languageEnglish (US)
Pages (from-to)1104-1113
Number of pages10
JournalGut
Volume55
Issue number8
DOIs
StatePublished - Aug 2006

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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    Adachi, M., Kurotani, R., Morimura, K., Shah, Y., Sanford, M., Madison, B. B., Gumucio, D. L., Marin, H. E., Peters, J. M., Young, H. A., & Gonzalez, F. J. (2006). Peroxisome proliferator activated receptor γ in colonic epithelial cells protects against experimental inflammatory bowel disease. Gut, 55(8), 1104-1113. https://doi.org/10.1136/gut.2005.081745