Peroxisome proliferator-activated receptor-alpha modulates the anti-inflammatory effect of glucocorticoids in a model of inflammatory bowel disease in mice.
Glucocorticoids (GCs) are effective anti-inflammatory agents widely used in therapeutic approach to treatment of inflammatory bowel disease (IBD). Previous results suggest that peroxisome proliferator-activated receptor [alpha] (PPAR-[alpha]), an intracellular transcription factor activated by fatty acids, plays a role in control of inflammation. With the aim to characterize the role of PPAR-[alpha] in GC-mediated anti-inflammatory activity, we tested the efficacy of dexamethasone (DEX), a synthetic GC specific for GR, in an experimental model of IBD induced by dinitrobenzene sulfonic acid, comparing mice lacking PPAR-[alpha] (PPAR-[alpha]KO) with wild-type (WT) mice. Results indicate that DEX-mediated anti-inflammatory activity is weakened in PPAR-[alpha]KO mice as compared with WT controls. In particular, DEX was less effective in PPAR-[alpha]KO compared with WT mice, as evaluated by inhibition of proinflammatory cytokines production, cell migration, oxidative stress, apoptosis, and colon injury. These results indicate that PPAR-[alpha] can contribute to the anti-inflammatory activity of GCs in IBD.
Riccardi
Luisa
L
Department of Clinical and Experimental Medicine, University of Perugia, Italy.
Mazzon
Emanuela
E
Bruscoli
Stefano
S
Esposito
Emanuela
E
Crisafulli
Concetta
C
Di Paola
Rosanna
R
Caminiti
Rocco
R
Riccardi
Carlo
C
Cuzzocrea
Salvatore
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001557:Benzenesulfonates / Q000633:toxicity; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000187:drug effects; D047493:PPAR alpha / Q000819:agonists* / Q000235:genetics / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D001557:Benzenesulfonates; D016207:Cytokines; D005938:Glucocorticoids; D018836:Inflammation Mediators; D047493:PPAR alpha; C007488:dinitrobenzenesulfonic acid; D003907:Dexamethasone