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 α (PPAR-α), an intracellular transcription factor activated by fatty acids, plays a role in control of inflammation. With the aim to characterize the role of PPAR-α 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-α (PPAR-αKO) with wild-type (WT) mice. Results indicate that DEX-mediated antiinflammatory activity is weakened in PPAR-αKO mice as compared with WT controls. In particular, DEX was less effective in PPAR-αKO 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-α can contribute to the anti-inflammatory activity of GCs in IBD.
Peroxisome proliferator-activated receptor-alpha modulates the anti-inflammatory effect of glucocorticoids in a model of inflammatory bowel disease in mice
RICCARDI, LUISA;BRUSCOLI, STEFANO;RICCARDI, Carlo;
2009
Abstract
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 α (PPAR-α), an intracellular transcription factor activated by fatty acids, plays a role in control of inflammation. With the aim to characterize the role of PPAR-α 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-α (PPAR-αKO) with wild-type (WT) mice. Results indicate that DEX-mediated antiinflammatory activity is weakened in PPAR-αKO mice as compared with WT controls. In particular, DEX was less effective in PPAR-αKO 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-α can contribute to the anti-inflammatory activity of GCs in IBD.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
