Cigarette smoking is associated with a series of lung diseases such as cancer, chronic obstructive
pulmonary disease (COPD), and asthma. Despite the intense interest, the underlying molecular mechanism in
smoking-related diseases is incompletely understood. Here, we show that Lyn is involved in cytotoxicity of
respiratory epithelial cells induced by cigarette smoke extracts (CSE), an in vitro culture model for evaluating
tobacco toxicity. In addition, exposure to CSE promotes the activation of JAK2 and STAT1, which is
responsible for CSE-induced cytotoxicity. Moreover, a Lyn specific siRNA, Lyn dominant negative construct
and pharmacological inhibitor all alleviated CSE-induced cytotoxicity in lung cells to different extents,
respectively. Furthermore, Lyn also influences the phagocytosis of bacteria by murine alveolar macrophages,
extending its impact on innate immunity. Taken together, these findings indicate that Lyn may play a role in the
regulation of cigarette smoking-induced lung cell death, and may be a potential novel therapeutic target for
cigarette smoking related lung diseases.
Cancer risk, COPD, cigarette smoke extract (CSE), cytotoxicity, JAK2, STAT1.
Department of Basic Sciences, University of North Dakota, Grand Forks, ND, USA.