Vanin-1 licenses inflammatory mediator production by gut epithelial cells and controls colitis by antagonizing peroxisome proliferator-activated receptor γ activity

作者：Carole Berruyer-Pouyet, Laurent Pouyet, Virginie Millet, Florent Martin, A. Legoffic, Alexandra Canonici, Stéphane Garcia, Claude Bagnis, Philippe Naquet, Franck Galland · 发表于：The Journal of Experimental Medicine · 年份：2006 · DOI：10.1084/jem.20061640 · 被引用次数：149 · 研究领域：Peroxisome Proliferator-Activated Receptors、Pharmacological Effects of Natural Compounds、Neurological diseases and metabolism

Colitis involves immune cell-mediated tissue injuries, but the contribution of epithelial cells remains largely unclear. Vanin-1 is an epithelial ectoenzyme with a pantetheinase activity that provides cysteamine/cystamine to tissue. Using the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-colitis model we show here that Vanin-1 deficiency protects from colitis. This protection is reversible by administration of cystamine or bisphenol A diglycidyl ether, a peroxisome proliferator-activated receptor (PPAR)gamma antagonist. We further demonstrate that Vanin-1, by antagonizing PPARgamma, licenses the production of inflammatory mediators by intestinal epithelial cells. We propose that Vanin-1 is an epithelial sensor of stress that exerts a dominant control over innate immune responses in tissue. Thus, the Vanin-1/pantetheinase activity might be a new target for therapeutic intervention in inflammatory bowel disease.