Cilostazol inhibits interleukin‐1‐induced ADAM17 expression through cAMP independent signaling in vascular smooth muscle cells

摘要: Increased A disintegrin and metalloprotease 17 (ADAM17) expression in vascular smooth muscle cells (VSMC) is implicated the development of cardiovascular diseases including atherosclerosis hypertension. Although cilostazol, type III phosphodiesterase (PDE III) inhibitor, has recently been found to inhibit VSMC proliferation, mechanisms remain largely unclear. Here, we hypothesized that cilostazol regulates ADAM17 VSMC. In cultured VSMC, interleukin (IL)-1α IL-1β significantly increased expression. MEK inhibitor U0126, NF-κB BAY-11-7085, siRNA targeting p65/RelA inhibited IL-1α or IL-β-induced Cilostazol IL-1β-induced extracellular signal-regulated kinase (ERK) phosphorylation Unexpectedly, cilostamide, dibutryl cAMP, forskolin did not affect IL-1-induced Our results clearly demonstrated IL-1 induces through ERK/NF-κB activation VSMCs. Moreover, inhibitory effects on may be independent cAMP signaling pathway These novel findings provide important clues understanding proliferation.