Nicotine induces apoptosis through exacerbation of blocked alveolar macrophage autophagic degradation in silicosis.

ABSTRACT

Silica dust mainly attacks alveolar macrophages (AMs). The apoptosis of AMs is correlated with the progress of silicosis. Our previous study showed that autophagic degradation was blocked in AMs from silicosis patients. However, the effects of nicotine on AM autophagy and apoptosis in silicosis are unknown. In this study, we collected AMs from twenty male workers exposed to silica and divided them into observer and silicosis patient groups, according to the tuberous pathological changes observed by X-ray. The AMs from both groups were exposed to nicotine. We found increased levels of LC3, p62, and cleaved caspase-3, decreased levels of LAMP2, and damaged lysosomes after nicotine stimulation of the AMs from both groups. We also found that the autophagy inhibitor 3-methyladenine (3MA) inhibited nicotine-induced apoptosis in the AMs. Furthermore, 3MA reversed both the nicotine-induced decrease in Bcl-2 and the increase in Bax in both groups. These results suggest that nicotine may induce apoptosis by blocking AM autophagic degradation in human silicosis.