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.

PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-alpha MODULATES THE ANTI-INFLAMMATORY EFFECT OF GLUCOCORTICOIDS IN A MODEL OF INFLAMMATORY BOWEL DISEASE IN MICE.

MAZZON, E;ESPOSITO, E;CRISAFULLI, C;DI PAOLA, R;CAMINITI, R;CUZZOCREA, S.
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 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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/1865879
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