Inhibitory effect of simvastatin on TNF-α-induced chemokines secretion in rheumatoid arthritis fibroblast like synoviocytes via inhibition of RhoA activation |
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| Authors: | CHEN Wei-ling LIANG Liu-qin QIU Qian YE Yu-jin ZHAN Zhong-ping |
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| Institution: | Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China |
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| Abstract: | AIM: To investigate the effect of simvastatin (SMV) on tumor necrosis factor α (TNF-α)-induced chemokine secretion in rheumatoid arthritis fibroblast-like synoviocytes (RA FLS).METHODS: RhoA activity was determined by pull-down assay. Chemokine secretion was measured by ELISA. MTT test was used to detect cell viability.RESULTS: Simvastatin attenuated TNF-α-induced interleukin-8(IL-8) and monocyte chemotactic protein-1(MCP-1) secretion as well as RhoA activation in RA FLS. The inhibitory effects of SMV were completely reversed by mevalonate (MEVA) and geranylgeranyl pyrophosphate (GGPP). Suppression of RhoA activation with a specific inhibitor depressed the secretion of IL-8 and MCP-1 in TNF-α-induced RA FLS.CONCLUSION: Simvastatin inhibits TNF-α-induced secretion of IL-8 and MCP-1 in RA FLS through inhibition of RhoA activation, indicating a novel strategy for anti-inflammatory effects of statins on treatment of RA. |
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| Keywords: | Simvastatin Arthritis rheumatoid Chemokines |
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