Etanercept conferred the protection effects from apoptosis induced by cigarette smoke in pulmonary arterial vascular endothelial cell

Rationale:Tobacco smoke-induced chronic obstructive pulmonary disease is a prolonged lung inflammatory condition due to a number of pathologic mechanisms, including pulmonary vascular remodeling. Endothelia cell apoptosis involved in this progress are unknown. Objectives: To determine whether TNF-α expression contribute to the pulmonary arterial vascular endothelial cell (HPAEC) apoptosis associated with tobacco smoke and assess the protective effect of TNF-α inhibitor Etanercept. Methods:Lung specimens from smokers with moderate COPD and without airflow obstruction were investigated by histology and immunohistochemistry.HPAEC was pre-incubated with Etanercept before exposed to cigarette smoke extract and the apoptosis molecular was investigated. Results:Compared with the non-smokers,lung of smokers with or without COPD showed a significant increase in TNF-α expression and apoptotic HPAEC,correlative to the smoke exposure.Furthermore, pre-treating with Etanercept reduced cigarette smoke extract-induced apoptosis in HPAEC through the activation of caspase cascades.Moreover, Etanercept inhibited cigarette smoke extract-induced Fas increase and regulated the balance between Bcl-2 and Bax. Conclusions:Our study showed a significant increase in TNF-α expression and apoptotic endothelia in smokers9 lungs.Etanercept conferred the protection effects from apoptosis induced by CSE in HPAEC largely depend on inhibiting activation of caspase cascades via the FAS-related and mitochondrial apoptotic pathways.Etanercept inhibited increase of Fas and activation of caspase-8.In the mitochondrial pathway,Etanercept regulated the Bcl-2/Bax balance.