RT Journal Article SR Electronic T1 Mechanism of the Anti-Inflammatory Effect of Thiazolidinediones: Relationship with the Glucocorticoid Pathway JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 1620 OP 1628 DO 10.1124/mol.104.004895 VO 67 IS 5 A1 Armando Ialenti A1 Gianluca Grassia A1 Paola Di Meglio A1 Pasquale Maffia A1 Massimo Di Rosa A1 Angela Ianaro YR 2005 UL http://molpharm.aspetjournals.org/content/67/5/1620.abstract AB The glucocorticoid receptor (GR) and peroxisome proliferator-activated receptors (PPARs) play important roles in both physiological and pathological conditions such as cell differentiation, lipolysis, control of glucose metabolism, immunity, and inflammation. In fact, recent studies suggest that the thiazolidinedione (TZD) class of PPAR-γ ligands, like glucocorticoids, may also be clinically beneficial in several inflammatory diseases, even if the molecular mechanisms responsible for these activities have not yet been clarified. In this study, by using a murine model of inflammation, the carrageenin-induced paw edema in mouse, we show that the anti-inflammatory activity exhibited by the PPAR-γ agonists rosiglitazone and ciglitazone is reversed by the GR antagonist RU486 (17β-hydroxy-11β-[4-dimethylamino phenyl]-17α-[1-propynyl]estra-4,9-dien-3-one). Moreover, by using a conditional GR null cell line, we demonstrate, for the first time to our knowledge, that one of the possible mechanisms explaining the anti-inflammatory activity of TZDs is their ability to activate GR nuclear translocation. In addition, by using J774 cell line lacking PPAR-γ, we demonstrate that PPAR-γ expression could not be essential for TZD-mediated GR nuclear translocation, thus explaining, at least in part, the molecular mechanism underlying their anti-inflammatory activity.