Activators of peroxisome proliferator-activated receptor-gamma (PPARgamma) inhibit inducible nitric oxide synthase expression but increase heme oxygenase-1 expression in rat glial cells.
The peroxisome proliferator-activated receptor-gamma (PPARgamma) is activated by 15-deoxy-delta(12,14) prostaglandin J2 (15d-PGJ2), anti-diabetic thiazolidinediones and several non-steroidal anti-inflammatory drugs (NSAIDs). In rat glial cells, lipopolysaccharide and interferon-gamma (LPS/IFN-gamma) induced expression of both inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1). PPARgamma activators inhibited iNOS expression by LPS and IFN-gamma. However, PPARgamma activator alone induced HO-1 expression and further enhanced LPS/IFN-gamma-induced HO-1 expression. These results suggest that activation of PPARgamma negatively regulate iNOS expression and positively regulates HO-1 expression in glial cells.
Kitamura
Y
Y
Department of Neurobiology, Kyoto Pharmaceutical University, Japan.
Kakimura
J
J
Matsuoka
Y
Y
Nomura
Y
Y
Gebicke-Haerter
P J
PJ
Taniguchi
T
T
D000077556:Alitretinoin; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D051547:Heme Oxygenase-1; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000819:agonists*; D014212:Tretinoin / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D009573:Nitrites; D011743:Pyrimidines; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077556:Alitretinoin; D014212:Tretinoin; D007371:Interferon-gamma; C006253:pirinixic acid; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D015232:Dinoprostone; D015230:Prostaglandin D2; C039671:ciglitazone