Repression of interferon-gamma-induced inducible nitric oxide synthase (iNOS) gene expression in microglia by sodium butyrate is mediated through specific inhibition of ERK signaling pathways.
We have reported recently that sodium butyrate suppressed IFN-gamma, but not the LPS-mediated induction of nitric oxide and TNF-alpha in microglia via the specific inhibition of NF-kappaB. In order to further determine the upstream signaling mechanism involved in the IFN-gamma-specific down-regulation of iNOS by sodium butyrate in microglia, this study investigated the effect of sodium butyrate on the MAP kinase activities. Sodium butyrate significantly repressed the phosphorylation of ERK induced by IFN-gamma, but had little effect on that induced by LPS. This suggests that sodium butyrate suppresses the IFN-gamma-induced iNOS expression by inhibiting the ERK to NF-kappaB pathway. In addition, it was found that sodium butyrate suppressed the IFN-gamma-induced interferon regulatory factor 1 (IRF-1) expression via the inhibition of ERK. Therefore, the ERK signaling pathway appears to play a key role in the sodium butyrate-mediated down-regulation of iNOS in the IFN-gamma-stimulated microglia.
Park
Jin-Sun
JS
Department of Neuroscience, Ewha Institute of Neuroscience, Ewha Womans University School of Medicine, 70 Jongno 6-Ga, Jongno-Gu, Seoul 110-783, South Korea.
Woo
Moon-Sook
MS
Kim
So-Young
SY
Kim
Won-Ki
WK
Kim
Hee-Sun
HS
D000704:Analysis of Variance; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D002087:Butyrates / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000201:enzymology; D008954:Models, Biological; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D014162:Transfection / Q000379:methods
D000998:Antiviral Agents; D002087:Butyrates; D004791:Enzyme Inhibitors; D005419:Flavonoids; D012333:RNA, Messenger; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one