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Peroxisome proliferator-activated receptor-gamma agonists suppress iNOS expression induced by LPS in rat primary Schwann cells.

Abstract
In bacterial-induced peripheral nervous system (PNS) inflammation, Schwann cells (SCs) are activated, producing inducible nitric oxide synthase (iNOS), contributed to the pathogenesis of demyelinating disease, such as multiple sclerosis. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has been shown to play a protective role in cellular inflammatory responses. Here we showed that LPS-induced iNOS biosynthesis was in a concentration and time-dependent manner. In LPS-treated primary SCs, retreatment with PPAR-gamma agonist remitted the increase of iNOS, p38 phosphorylation and TLR4, MyD88, augmented the expression of PPAR-gamma and localization in nuclear. Coadministration of GW 9662 reversed the effect of PPAR-gamma agonists. These results suggest that PPAR-gamma agonists, 15d-PGJ(2) and pioglitazone, had the anti-inflammatory effects.
AuthorsFupeng Zhang, Fen Liu, Meijuan Yan, Huoyan Ji, Ling Hu, Xiaohong Li, Ji Qian, Xingxin He, Li Zhang, Aiguo Shen, Chun Cheng
JournalJournal of neuroimmunology (J Neuroimmunol) Vol. 218 Issue 1-2 Pg. 36-47 (Jan 25 2010) ISSN: 1872-8421 [Electronic] Netherlands
PMID19942298 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2009 Elsevier B.V. All rights reserved.
Chemical References
  • 15-deoxyprostaglandin J2
  • 2-chloro-5-nitrobenzanilide
  • Anilides
  • Anti-Inflammatory Agents
  • Enzyme Inhibitors
  • Lipopolysaccharides
  • Myd88 protein, rat
  • Myeloid Differentiation Factor 88
  • PPAR gamma
  • Thiazolidinediones
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Nitric Oxide Synthase Type II
  • p38 Mitogen-Activated Protein Kinases
  • Prostaglandin D2
  • Pioglitazone
Topics
  • Anilides (pharmacology)
  • Animals
  • Anti-Inflammatory Agents (pharmacology)
  • Blotting, Western
  • Cell Line
  • Down-Regulation
  • Enzyme Inhibitors (pharmacology)
  • Fluorescent Antibody Technique
  • Lipopolysaccharides (pharmacology)
  • Myeloid Differentiation Factor 88 (biosynthesis, drug effects)
  • Nitric Oxide Synthase Type II (biosynthesis, drug effects)
  • PPAR gamma (agonists, drug effects)
  • Pioglitazone
  • Prostaglandin D2 (analogs & derivatives, pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Schwann Cells (metabolism)
  • Signal Transduction (drug effects, physiology)
  • Thiazolidinediones (pharmacology)
  • Toll-Like Receptor 4 (biosynthesis, drug effects)
  • p38 Mitogen-Activated Protein Kinases (drug effects, metabolism)

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