Rosiglitazone, a ligand of the peroxisome proliferator-activated receptor-γ, reduces acute inflammation

Cuzzocrea, S., Pisano, B., Dugo, L., Ianaro, A, Maffia, P., Patel, N.S.A., Di Paola, R., Ialenti, A., Genovese, T., Chatterjee, P.K., Di Rosa, M., Caputi, A.P. and Thiemermann, C. (2004) Rosiglitazone, a ligand of the peroxisome proliferator-activated receptor-γ, reduces acute inflammation European journal of pharmacology, 483 (1). pp. 79-93. ISSN 0014-2999

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Official URL: http://dx.doi.org/10.1016/j.ejphar.2003.10.056

Abstract

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors that are related to retinoid, steroid and thyroid hormone receptors. The PPAR-γ receptor subtype appears to play a pivotal role in the regulation of cellular proliferation and inflammation. The thiazolidinedione rosiglitazone (Avandia) is a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, that was recently approved by the Food and Drug Administration for treatment of type II diabetes mellitus. In the present study, we have investigated the effects of rosiglitazone in animal models of acute inflammation (carrageenan-induced paw oedema and carrageenan-induced pleurisy). We report here for the first time that rosiglitazone (given at 1, 3 or 10 mg/kg i.p. concomitantly with carrageenan injection in the paw oedema model, or at 3, 10 or 30 mg/kg i.p. 15 min before carrageenan administration in the pleurisy model) exerts potent anti-inflammatory effects (e.g. inhibition of paw oedema, pleural exudate formation, mononuclear cell infiltration and histological injury) in vivo. Furthermore, rosiglitazone reduced: (1) the increase in the staining (immunohistochemistry) for nitrotyrosine and poly (ADP-ribose) polymerase (PARP), (2) the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), intercellular adhesion molecules-1 (ICAM-1) and P-selectin in the lungs of carrageenan-treated rats. In order to elucidate whether the protective effect of rosiglitazone is related to activation of the PPAR-γ receptor, we also investigated the effect of a PPAR-γ antagonist, bisphenol A diglycidyl ether (BADGE), on the protective effects of rosiglitazone. BADGE (30 mg/kg i.p.) administered 30 min prior to treatment with rosiglitazone significantly antagonized the effect of the PPAR-γ agonist and thus abolished the anti-inflammatory effects of rosiglitazone. We propose that rosiglitazone and other potent PPAR-γ agonists may be useful in the therapy of inflammation.

Item Type:Journal article
Uncontrolled Keywords:PPAR (peroxisome proliferator-activated receptor); Rosiglitazone; Inflammation, acute; iNOS (nitric oxide synthase inducible); Cyclooxygenase-2; ICAM-1 (intercellular adhesion molecule-1)
Subjects:B000 Health Professions > B100 Anatomy Physiology and Pathology
DOI (a stable link to the resource):10.1016/j.ejphar.2003.10.056
Faculties:Faculty of Science and Engineering > School of Pharmacy and Biomolecular Sciences
ID Code:433
Deposited By:editor spbs
Deposited On:08 Nov 2007
Last Modified:18 Jun 2010 12:28

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