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 a (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.