Inhibition of lovastatin on proliferation and expression of proinflammatory cytokines in cultured human glomerular mesangial cells.
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.


CONCLUSIONS
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.
Li
Hang
H
Department of Nephrology, Peking Union Medical College Hospital, Beijing 100730, China.
Li
Xuewang
X
Duan
Lin
L
Li
Chenhong
C
D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000032:analysis*; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis*; D015850:Interleukin-6 / Q000032:analysis*; D008148:Lovastatin / Q000494:pharmacology*; D016328:NF-kappa B; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D018932:Chemokine CCL2; D007375:Interleukin-1; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D008148:Lovastatin