Objective: To investigate whether the effect of smoking on airway smooth muscle cells (ASMC) is mediated by the autocrine action of endothelin-1 (ET-1).
Methods: Abbit ASMC was cultured exposed to cigarette smoke extract (CSE), we examined the mitogenic effect CSE on ASMC in vitro and whether the ETA receptor antagonist JKC-301 can inhibit this effect.
Results: The exposure of ASMC to 10% and 30% CSE resulted in obvious cytotoxity. The viability of ASMC was decreased, the lipid peroxides (MDA) formation was increased, and the release of lactate dehydrogenase (LDH) into supernatant was enhanced. 5% CSE significantly enhanced the cultured ASMC[3H]-thymidine (3H-TdR) incorporation by 59.9% (P < 0.01) over control. The ASMC proliferative response to 5% CSE was dose-dependently inhibited by JKC-301. Moreover, 5% CSE evoked time-dependent release of endogenous ET-1 from ASMC.
Conclusion: These data demonstrate that 5% CSE mediates ASMC proliferation via release and autocrine mitogenic action ET-1.