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Statins induce suppressor of cytokine signaling‐3 in macrophages
Author(s) -
Huang Kuo-Chin,
Chen Ching-Wen,
Chen Jui-Ching,
Lin Wan-Wan
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)01297-3
Subject(s) - protein kinase a , janus kinase , ask1 , stat protein , microbiology and biotechnology , kinase , biology , signal transduction , mitogen activated protein kinase kinase , chemistry , stat3
Our previous study has shown that lipophilic 3‐hydroxy‐3‐methyl‐glutaryl coenzyme A reductase inhibitors of statins can inhibit interferon‐γ‐induced inducible nitric oxide synthase gene expression in RAW264.7 macrophages. In this study, we showed that lovastatin and fluvastatin are able to upregulate the mRNA expression of the suppressor of cytokine signaling‐3 (SOCS‐3) gene. This effect is specific for SOCS‐3 and could be blocked by mevalonate, farnesyl pyrophosphate and geranylgeranyl pyrophosphate, while it was not affected by inhibitors of protein kinase C and A, mitogen‐activated protein/extracellular signal‐regulated kinase kinase, p38 mitogen‐activated protein kinase, c‐Jun N‐terminal kinase, Src, Raf and Rho kinase. SOCS‐3 expression results in the inhibition of interferon‐γ‐, interleukin‐6‐ and macrophage colony‐stimulating factor‐elicited signal transducer and activator of transcription phosphorylation, suggesting a novel anti‐inflammatory mechanism of statins to down‐modulate the functions of interferon‐γ‐activated macrophages.