Inhibition of double-stranded RNA-induced inducible nitric oxide synthase expression by fraxinellone and sauchinone in murine microglia.
Fraxinellone and sauchinone, isolated from natural substance, are known to have an anti-inflammatory effect in inflammatory conditions. However, the anti-inflammatory actions of these compounds have been insufficiently demonstrated in viral-induced neuroinflammation. A viral component (double-stranded (ds)RNA) triggers a toll-like receptor 3-dependent inflammatory response that stimulates pro-inflammatory mediators in the brain. In present study, we initially examined the biological effects of fraxinellone and sauchinone on anti-inflammatory actions in dsRNA-stimulated microglia. Both compounds inhibited dsRNA-induced inducible nitric oxide synthase (iNOS) expression, a major pro-inflammatory enzyme. To demonstrate the mechanism of inhibitory effect on iNOS expression, we further examined the signaling pathway induced by dsRNA in microglia. Our data show that dsRNA promotes the expression of signal transducers and activators of transcription (STAT)1/3 identified as major inflammatory transcription factors as well as activates c-Jun N-terminal kinase (JNK) in an early time. Moreover, both compounds suppressed activation of JNK-STAT1/3 signaling pathway. These results suggest that an anti-inflammatory effect by fraxinellone and sauchinone is mediated via blockade of the JNK-STAT1/3-iNOS signaling pathway in viral-infected microglia.
Lee
Chang Seok
CS
Department of Pharmacology, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 110-799, Korea.
Won
Cheolhee
C
Yoo
Hyouna
H
Yi
Eun Hee
EH
Cho
Yuri
Y
Maeng
Jung Woo
JW
Sung
Sang Hyun
SH
Ye
Sang-Kyu
SK
Chung
Myung-Hee
MH
D000818:Animals; D001483:Base Sequence; D001572:Benzofurans / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D015153:Blotting, Western; D017931:DNA Primers; D004149:Dioxoles / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000201:enzymology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000502:physiology*; D051196:Toll-Like Receptor 3 / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
D001572:Benzofurans; D001578:Benzopyrans; D017931:DNA Primers; D004149:Dioxoles; D012330:RNA, Double-Stranded; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; C410958:sauchinone; C075391:fraxinellone; D052247:Nitric Oxide Synthase Type II