Vanin-1 licenses inflammatory mediator production by gut epithelial cells and controls colitis by antagonizing peroxisome proliferator-activated receptor gamma activity.
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.
Berruyer
Carole
C
Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, 13288 Marseille Cedex 9, France.
Pouyet
Laurent
L
Millet
Virginie
V
Martin
Florent M
FM
LeGoffic
Aude
A
Canonici
Alexandra
A
Garcia
Stéphane
S
Bagnis
Claude
C
Naquet
Philippe
P
Galland
Franck
F
D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology; D000581:Amidohydrolases; D000818:Animals; D001559:Benzhydryl Compounds; D001835:Body Weight; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D054426:Chemokine CXCL2; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003538:Cystamine / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D004852:Epoxy Compounds / Q000494:pharmacology; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation / Q000187:drug effects; D053583:Interleukin-1beta / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D016019:Survival Analysis; D014302:Trinitrobenzenesulfonic Acid; D000098826:Bisphenol A Compounds
D000581:Amidohydrolases; D001559:Benzhydryl Compounds; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D054426:Chemokine CXCL2; D018925:Chemokines; D051546:Cyclooxygenase 2; D003538:Cystamine; D016207:Cytokines; D004852:Epoxy Compounds; D058851:GPI-Linked Proteins; D053583:Interleukin-1beta; D047495:PPAR gamma; D015230:Prostaglandin D2; D014302:Trinitrobenzenesulfonic Acid; C477819:15-deoxyprostaglandin J2; C491768:Ccl2 protein, mouse; C404915:Cxcl2 protein, mouse; C022314:pantetheinase; C019273:bisphenol A diglycidyl ether; D000098826:Bisphenol A Compounds