OBJECTIVE: To study the effects and mechanism of lovastatin on cell proliferation and expression of proinflammatory cytokines in cultured human glomerular mesangial cells. METHODS: The influence of lovastatin on HMC proliferation was evaluated with 3H-thymidine incorporation. mRNA expression of proinflammatory cytokines (IL-1 beta, IL-6, TNF-alpha, and MCP-1) and activation of NF-kappa B of HMC were measured using Reverse transcription-polymerase chain reaction (RT-PCR) and electrophoretic mobility shift assay (EMSA) respectively. RESULTS: Lovastatin was found to have inhibitory effects on human mesangial cell (HMC) proliferation and lipopolysaccharide (LPS)-mediated human mesangine cell HMC mRNA expression of proinflammatory cytokines via activation of NF-kappa B. The effect of lovstatin on HMC could be prevented when the mevalonate and farnesol were added to the culture. CONCLUSION: Lovastatin may decrease HMC proliferation and production of proinflammatory cytokines through the inhibition of NF-kappa B activation. This provided experimental evidence for further evaluation of the renal protective effect of HRI, suggesting that it may be a potent agent for prevention of progressive renal diseases aside from its lipid-lowering effect.
OBJECTIVE: To study the effects and mechanism of lovastatin on cell proliferation and expression of proinflammatory cytokines in cultured human glomerular mesangial cells. METHODS: The influence of lovastatin on HMC proliferation was evaluated with 3H-thymidine incorporation. mRNA expression of proinflammatory cytokines (IL-1 beta, IL-6, TNF-alpha, and MCP-1) and activation of NF-kappa B of HMC were measured using Reverse transcription-polymerase chain reaction (RT-PCR) and electrophoretic mobility shift assay (EMSA) respectively. RESULTS:Lovastatin was found to have inhibitory effects on human mesangial cell (HMC) proliferation and lipopolysaccharide (LPS)-mediated human mesangine cell HMC mRNA expression of proinflammatory cytokines via activation of NF-kappa B. The effect of lovstatin on HMC could be prevented when the mevalonate and farnesol were added to the culture. CONCLUSION:Lovastatin may decrease HMC proliferation and production of proinflammatory cytokines through the inhibition of NF-kappa B activation. This provided experimental evidence for further evaluation of the renal protective effect of HRI, suggesting that it may be a potent agent for prevention of progressive renal diseases aside from its lipid-lowering effect.