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PPAR-alpha activators suppress STAT1 inflammatory signaling in lipopolysaccharide-activated rat glia.

Authors
Lee, JH; Joe, EH; Jou, I
Citation
Neuroreport, 16(8):829-833, 2005
Journal Title
Neuroreport
ISSN
0959-49651473-558X
Abstract
Signal transducers and activators of transcription (STATs) have recently been reported to mediate glial activation, and thus potentially play important roles in many neuroinflammatory diseases. We examined the effect of peroxisome proliferator-activated receptor (PPAR) activators on inflammatory responses in cultured rat brain glial cells. Four PPAR-alpha activators were tested, three fibrates (WY14643, clofibrate and fenofibrate) and an arachidonic acid derivative (5,8,11,14-eicosatetraynoic acid). We found that all four PPAR-alpha activators suppressed lipopolysaccharide-stimulated STAT1 phosphorylation and nuclear factor binding to gamma-interferon-activated sequence/interferon-alpha-stimulated response element sites known to contain STAT binding sites. PPAR-alpha activators also suppressed lipopolysaccharide-stimulated tumor necrosis factor-alpha and monocyte chemoattractant protein-1 transcription and release. These results suggest that PPAR-alpha activators may be useful in the treatment of inflammatory brain diseases.
MeSH terms
AnimalsAnimals, NewbornArachidonic Acids/pharmacologyBlotting, Western/methodsCells, CulturedChemokine CCL2/metabolismClofibric Acid/pharmacologyDNA-Binding Proteins/metabolism*Dose-Response Relationship, DrugDrug InteractionsElectrophoretic Mobility Shift Assay/methodsEnzyme Activation/drug effectsEnzyme-Linked Immunosorbent Assay/methodsInflammation/metabolismLipopolysaccharides/pharmacology*Models, BiologicalNeuroglia/drug effects*Neuroglia/metabolismPPAR alpha/metabolism*Phosphorylation/drug effectsRNA, Messenger/biosynthesisRatsRats, Sprague-DawleyReverse Transcriptase Polymerase Chain Reaction/methodsSTAT1 Transcription FactorSignal Transduction/physiology*Trans-Activators/metabolism*Tumor Necrosis Factor-alpha/metabolism
PMID
15891579
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
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