title: Involvement of glucocorticoid receptor activation on anti-inflammatory effect induced by peroxisome proliferator-activated receptor γ agonist in mice.
abstract: Glucocorticoids are effective anti-inflammatory agents widely used for the treatment of acute and chronic inflammatory diseases. Recent in vitro studies have proposed that glucocorticoid receptor (GR) activation is involved in peroxisome proliferator-activated receptor γ (PPARγ) agonist-induced effects. In this study, to examine the involvement of the GR in PPARγ agonist- and retinoid X receptor (RXR) agonist-mediated anti-inflammatory effects in vivo, we tested the anti-inflammatory effects of dexamethasone (a GR agonist) with pioglitazone (a PPARγ agonist) or 6-[N-ethyl-N-(3-isopropoxy-4-isopropylphenyl)-amino] nicotinic acid (NEt-3IP; an RXR agonist) by using an experimental model of carrageenan-induced inflammation. We also evaluated the effects of a GR antagonist on PPARγ agonist- or RXR agonist-induced anti-inflammatory effects. Results showed that the GR antagonist RU486 reduced the anti-inflammatory effects of GR or PPARγ agonists but not those of the RXR agonist. In addition, combinations of GR and PPARγ agonists or GR and RXR agonists had no effect on carrageenan-induced paw edema. Moreover, the PPARγ antagonist GW9662 and RXR antagonist 6-[N-4-(trifluoromethyl)-benzenesulfonyl-N-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-amino] nicotinic acid (NS-4TF) had no effect on the anti-inflammatory effect of the GR agonist dexamethasone. Therefore, it is suggested that GR activation in vivo does not play a direct role in PPARγ/RXR heterodimer signaling. In contrast, pioglitazone showed a partial anti-inflammatory effect via GR activation. These data provide evidence for the pro-inflammatory activity of pioglitazone.
authors: Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Tsushima-naka 1-1-1, Kita-ku, Okayama 700-8530, Japan.
authors: Atsuki
authors: A
authors: Yamamoto
authors: Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Tsushima-naka 1-1-1, Kita-ku, Okayama 700-8530, Japan.
authors: Hiroki
authors: H
authors: Kakuta
authors: Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Tsushima-naka 1-1-1, Kita-ku, Okayama 700-8530, Japan. Electronic address: sugimoto@pharm.okayama-u.ac.jp.
authors: Yukio
authors: Y
authors: Sugimoto
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D002351:Carrageenan / Q000008:administration & dosage; D003907:Dexamethasone / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D015735:Mifepristone / Q000494:pharmacology; D023421:Models, Animal; D047495:PPAR gamma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077205:Pioglitazone; D011726:Pyridinium Compounds / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047488:Retinoid X Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013343:Styrenes / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D047495:PPAR gamma; D011726:Pyridinium Compounds; D011965:Receptors, Glucocorticoid; D047488:Retinoid X Receptors; D013343:Styrenes; D045162:Thiazolidinediones; C079700:N-ethyl-N-(4-(2-(4-(1-methylpyridino))ethenyl)phenyl)glycine N-hydroxysuccinimide ester; D015735:Mifepristone; D003907:Dexamethasone; D002351:Carrageenan; D000077205:Pioglitazone
keywords: Carrageenan; Glucocorticoid receptor; Inflammation; Peroxisome proliferator activated receptor γ; Retinoid X receptor