Simvastatin Inhibited the IL‐5–Induced Chemotaxis toward Eotaxin and CCR3 Expression of HL‐60–Derived Eosinophils

Abstract

Objectives: IL-5-induced chemotaxis of eosinophils is an important feature for atopic diseases. Lipid lowering agents, statins, have been shown with inhibitory ability for inflammatory process and leukocyte accumulation. We herein investigate their effects on chemotaxis of eosinophils and the possible regulating mechanisms. Methods: Eosinophils were derived by treating HL-60 clone 15 (HC15) with butyric acid in an alkaline condition. The 2 most potent chemokine and cytokine receptors for eosinophils, CC-chemokine receptor-3 (CCR3) and IL-5 receptor (IL5R), were verified on the cell line. Dose effect of IL-5 stimulation for chemotactic ability toward eotaxin and CCR3 presentation was measured. Simvastatin effect for IL-5 induced chemotaxis and these two receptors was analyzed in RNA and protein level. Mevalonate effect for the behaviors of simvastatin was also evaluated. Results: IL-5 in the dosage of 10 ng/mL had the most impressive enhancement on chemotaxis and CCR3 presentation for eosinophils harvested from HC15. Simvastatin inhibited IL-5-induced chemotaxis and CCR3 presentation in both mRNA and protein level but had no effect on IL5R. Mevalonate could reverse those inhibitory effects of simvastatin. Conclusions: Simvastatin inhibited IL-5-induced chemotaxis of HC15-derived eosinophils by repression of CCR3 presentation instead of IL5R. This inhibitory effect of simvastatin acted via mevalonate pathway which could be reversed by mevalonate replacement.