Statins induce suppressor of cytokine signaling‐3 in macrophages

FEBS Letters

Huang, Kuo-Chin¹  Chen, Jui-Ching²  Chen, Ching-Wen²  Lin, Wan-Wan² 

[1] Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan;Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan

关键词: Statin;    Suppressor of cytokine signaling-3;    Signal transducer and activator of transcription;    Interferon-γ;    Macrophage;    DMEM;    Dulbecco's modified Eagle's medium;    ERK;    extracellular signal-regulated kinase;    FPP;    farnesyl pyrophosphate;    GGPP;    geranylgeranyl pyrophosphate;    IFN-γ;    interferon-γ;    IL-6;    interleukin-6;    JAK;    Janus kinase;    MAPK;    mitogen-activated protein kinase;    M-CSF;    macrophage colony-stimulating factor;    MEK;    mitogen-activated protein/ERK kinase;    NOS;    nitric oxide synthase;    PKA;    protein kinase A;    PKC;    protein kinase C;    RT-PCR;    reverse transcription-polymerase chain reaction;    SOCS;    suppressor of cytokine signaling;    STAT;    signal transducer and activator of transcription;   

DOI  :  10.1016/S0014-5793(03)01297-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown