Peroxisome proliferation-activated receptor (PPAR)gamma is not necessary for synthetic PPARgamma agonist inhibition of inducible nitric-oxide synthase and nitric oxide

The Journal of Pharmacology and Experimental Therapeutics
Michelle B CrosbyGary S Gilkeson

Abstract

Peroxisome proliferation-activated receptor (PPAR)gamma agonists inhibit inducible nitric-oxide synthase (iNOS), tumor necrosis factor-alpha, and interleukin-6. Because of these effects, synthetic PPARgamma agonists, including thiazolidinediones, are being studied for their impact on inflammatory disease. The anti-inflammatory concentrations of synthetic PPARgamma agonists range from 10 to 50 microM, whereas their binding affinity for PPARgamma is in the nanomolar range. The specificity of synthetic PPARgamma agonists for PPARgamma at the concentrations necessary for anti-inflammatory effects is thus in question. We report that PPARgamma is not necessary for the inhibition of iNOS by synthetic PPARgamma agonists. RAW 264.7 macrophages possess little PPARgamma, yet lipopolysaccharide (LPS)/interferon (IFN)gamma-induced iNOS was inhibited by synthetic PPARgamma agonists at 20 microM. Endogenous PPARgamma was inhibited by the transfection of a dominant-negative PPARgamma construct into murine mesangial cells. In the transfected cells, synthetic PPARgamma agonists inhibited iNOS production at 10 microM, similar to nontransfected cells. Using cells from PPARgamma Cre/lox conditional knockout mice, baseline and LPS/IFNgamma-induced n...Continue Reading

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Citations

Jun 14, 2005·Molecular Immunology·Michelle B CrosbyTamara K Nowling
Sep 5, 2008·The Journal of Biological Chemistry·Brian M NecelaE Aubrey Thompson
Dec 29, 2009·PPAR Research·Christine Linard, Maâmar Souidi
Jul 11, 2008·PPAR Research·Brian M Necela, E Aubrey Thompson
Mar 1, 2006·Expert Opinion on Investigational Drugs·Jerry R Colca, Rolf F Kletzien
Sep 14, 2006·Fundamental & Clinical Pharmacology·Julien BeckerFrançoise Pons
Dec 21, 2006·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·M SpearsN C Thomson
Sep 29, 2005·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Ji-Nan SheuKai-Li Liu
Dec 20, 2011·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·María-Nieves SanzGloria Rodríguez-Villanueva
Nov 21, 2007·FEBS Letters·Attila Szanto, Tamás Roszer
Jun 6, 2006·Medicinal Research Reviews·Ana OlmosSalvador Máñez
Apr 11, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Yumei YeYochai Birnbaum
Jun 27, 2006·American Journal of Physiology. Gastrointestinal and Liver Physiology·Liu YangDon C Rockey
Oct 22, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Yumei YeYochai Birnbaum
Apr 1, 2006·The Journal of Pharmacology and Experimental Therapeutics·Hiroyuki KinoshitaYoshio Hatano
Mar 10, 2016·Immunopharmacology and Immunotoxicology·Vijay Kumar Reddy Kondreddy, Akhilender Naidu Kamatham
Apr 22, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anagha MalurMary Jane Thomassen

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