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Falcarindiol impairs the expression of inducible nitric oxide synthase by abrogating the activation of IKK and JAK in rat primary astrocytes
Author(s) -
Shiao YoungJi,
Lin YunLian,
Sun YaHui,
Chi ChihWen,
Chen ChiehFu,
Wang ChuenNeu
Publication year - 2005
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706022
Subject(s) - nitric oxide , nitric oxide synthase , chemistry , stat1 , stat protein , signal transduction , phosphorylation , biochemistry , janus kinase , tyrosine phosphorylation , pharmacology , stat3 , biology , organic chemistry
1 The effects of falcarindiol on the expression of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide/interferon‐ γ (LPS/IFN‐ γ ) in rat primary astrocytes were investigated. The molecular mechanisms underlying falcarindiol that confers its effect on iNOS expression were also elucidated. 2 Falcarindiol abrogated the LPS/IFN‐ γ ‐mediated induction of iNOS by about 80%. Falcarindiol attenuated the induction of iNOS in a concentration‐dependent manner. 3 The inhibitory effect of falcarindiol on iNOS induction was attributable to decrease in the protein content and the mRNA level of iNOS. 4 Treatment with 50 μ M of falcarindiol for 30 min decreased LPS/IFN‐ γ ‐induced nuclear factor‐ κ B (NF‐ κ B) activation by 32%. 5 Treatment with 50 μ M of falcarindiol for 60 min diminished the LPS/IFN‐ γ ‐mediated activation of I κ B kinase‐ α (IKK‐ α ) and IKK‐ β by 28.2 and 29.7%, respectively. 6 Falcarindiol modulated the nuclear translocation of signal transducer and activator of transcription 1 (Stat1) in a time‐dependent manner. Falcarindiol (50 μ M ) decreased the tyrosine phosphorylation of janus kinase 1 (JAK1) by 84.8% at 5 min. Falcarindiol also abrogated the tyrosine phoshorylation of JAK2 by 82.3% at 10 min. 7 The present study demonstrates that falcarindiol attenuated the activation of IKK and JAK contributing to the blockade of activation of NF‐ κ B and Stat1, thereby leading to the suppression of iNOS expression.British Journal of Pharmacology (2005) 144 , 42–51. doi: 10.1038/sj.bjp.0706022