Benzo[a] pyrene activates interleukin-6 induction and suppresses nitric oxide-induced apoptosis in rat vascular smooth muscle cells

Benzo[a] pyrene, a ubiquitous environmental pollutant, has been suggested to be capable of initiating and/or accelerating atherosclerosis. Accumulation of vascular smooth muscle cells (VSMCs) in vessel intima is a hallmark of atherosclerosis. Nitric oxide (NO) can suppress VSMCs proliferation and induce VSMCs apoptosis. NO plays a compensatory role in the vascular lesions to reduce proliferation and/or accelerate apoptosis of VSMCs. The aim of this study was to investigate whether benzo[a] pyrene can affect VSMCs growth and apoptosis induced by NO. Benzo[a] pyrene (1-30 mu mol/L) did not affect the cell number and cell cycle distribution in VSMCs under serum deprivation condition. Sodium nitroprusside (SNP), a NO donor, decreased cell viability and induced apoptosis in VSMCs. Benzo[a] pyrene significantly suppressed SNP-induced cell viability reduction and apoptosis. VSMCs cultured in conditioned medium from cells treated with benzo[a] pyrene could also prevent SNP-induced apoptosis. Benzo[a] pyrene was capable of inducing the activation of nuclear factor (NF)-kappa B and phosphorylation of p38 mitogen-activated protein kinase (MAPK) in VSMCs. Both NF-kappa B inhibitor and p38 MAPK inhibitor significantly reversed the anti-apoptotic effect of benzo[a] pyrene on SNP-treated VSMCs. Incubation of VSMCs with benzo[a] pyrene significantly and dose-dependently increased interleukin (IL)-6 production. A neutralizing antibody to IL-6 effectively reversed the anti-apoptotic effect of benzo[a] pyrene on SNP-treated VSMCs. Taken together, these results demonstrate for the first time that benzo[a] pyrene activates IL-6 induction and protects VSMCs from NO-induced apoptosis. These findings propose a new mechanism for the atherogenic effect of benzo[a] pyrene.