title: Lyn regulates cytotoxicity in respiratory epithelial cells challenged by cigarette smoke extracts.
abstract: 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.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Ye
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.forename: D
authors.initials: D
authors.lastname: Tan
authors.forename: Y
authors.initials: Y
authors.lastname: Jin
authors.forename: E
authors.initials: E
authors.lastname: Wu
authors.forename: Q
authors.initials: Q
authors.lastname: Cui
authors.affiliation: Department of Basic Sciences, University of North Dakota, Grand Forks, ND, USA. min.wu@med.und.edu.
authors.forename: M
authors.initials: M
authors.lastname: Wu
mesh_terms: D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects; D050794:STAT1 Transcription Factor / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*; D014026:Nicotiana
chemical_list: D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D012906:Smoke; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases