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Vanin-1 licenses inflammatory mediator production by gut epithelial cells and controls colitis by antagonizing peroxisome proliferator-activated receptor gamma activity.
- Source :
-
The Journal of experimental medicine [J Exp Med] 2006 Dec 25; Vol. 203 (13), pp. 2817-27. Date of Electronic Publication: 2006 Dec 04. - Publication Year :
- 2006
-
Abstract
- 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.
- Subjects :
- Active Transport, Cell Nucleus drug effects
Active Transport, Cell Nucleus physiology
Amidohydrolases
Animals
Benzhydryl Compounds
Body Weight
Cell Adhesion Molecules deficiency
Cell Adhesion Molecules genetics
Cell Line
Cell Nucleus drug effects
Cell Nucleus metabolism
Chemokine CCL2 genetics
Chemokine CCL2 metabolism
Chemokine CXCL2
Chemokines genetics
Chemokines metabolism
Colitis chemically induced
Colitis pathology
Colon drug effects
Colon metabolism
Colon pathology
Cyclooxygenase 2 metabolism
Cystamine pharmacology
Cytokines genetics
Cytokines metabolism
Epithelial Cells drug effects
Epoxy Compounds pharmacology
GPI-Linked Proteins
Gene Expression Regulation drug effects
Interleukin-1beta pharmacology
Mice
Mice, Inbred BALB C
Mice, Knockout
Mice, SCID
PPAR gamma antagonists & inhibitors
PPAR gamma genetics
Prostaglandin D2 analogs & derivatives
Prostaglandin D2 pharmacology
Survival Analysis
Trinitrobenzenesulfonic Acid
Cell Adhesion Molecules physiology
Colitis metabolism
Epithelial Cells metabolism
PPAR gamma metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1007
- Volume :
- 203
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 17145956
- Full Text :
- https://doi.org/10.1084/jem.20061640