Effects of cigarette smoke extract on surfactant production in ATII-like cells, involvement of oxidative stress and autophagy

Surfactant plays an essential role in pulmonary physiology by reducing surface tension, preventing alveolar collapse, and regulating immune responses in the lung. The composition and function of surfactant can be modified by environmental pollutants. Among these, cigarette smoke is a leading cause of respiratory and cardiovascular diseases. However, the impact of cigarette smoke on surfactant composition and function is still poorly understood. This study evaluated the effects of cigarette smoke extract (CSE) on surfactant production in a differentiated cell model (A549/ATII-like). Specifically, we evaluated the effects of CSE on multilamellar bodies (MLBs) involved in surfactant synthesis and storage, lipid production and secretion, surface tension, and the expression of the surfactant proteins SP-B and SP-C. Since autophagy is involved in MLBs maturation, the expression of SQSTM1/p62 and of the phosphorylated protein pATG-16L1^S278 was evaluated to assess the effect of CSE exposure on the induction of the early stages of the autophagic process. Our results demonstrated that CSE exposure affects the expression of surfactant components in A549/ATII-like cells, inducing an increase in the surface tension at the air-water interface, possibly via oxidative stress and the alteration of autophagy.