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.