Cigarette smoke extract induces apoptosis of rat alveolar Type II cells via the PLTP/TGF-β1/Smad2 pathway.

Apoptosis of alveolar epithelial cells has been implicated in the pathogenesis of acute lung injury. Phospholipid transfer protein (PLTP) may play a role in apoptosis. In the present study, the effect of the novel function of PLTP in cigarette smoke extract (CSE)-induced apoptosis of alveolar epithelial cells and the possible mechanism were examined. Male Wistar rats were exposed to air and cigarette smoke (n=10/exposure) for 6h/day on 3 consecutive days, then the lungs were sectioned and examined. To investigate effects on alveolar epithelial cells, rat alveolar epithelial cells (RLE-6TN) were treated with different concentrations of CSE for various times. siRNA for PLTP was transfected into cells and an inhibitor of the transforming growth factor-β1 (TGF-β1) type I receptor was administered prior to CSE exposure. Apoptosis was measured, and mRNA expression of PLTP and TGF-β1 and protein levels of PLTP, TGF-β1, p-Smad2 and cleaved caspase-3 were analyzed. The results showed that apoptosis, as well as expression of PLTP, TGF-β1, p-Smad2 and cleaved caspase-3 were all significantly increased after CSE stimulation (P<0.05). Furthermore, the expression of TGF-β1, p-Smad2 and cleaved caspase-3 induced by CSE could be partly abrogated by knockdown of PLTP. The expression of PLTP showed no significant change as a result of TGF-β1 receptor inhibition, while cleaved caspase-3 showed a remarkable reduction. PLTP may act as an upstream signal molecule of the TGF-β1/Smad2 pathway and is likely to be involved in CSE-induced apoptosis of alveolar epithelial cells.