Cigarette smoke induces growth differentiation factor 15 production in human lung epithelial cells: implication in mucin over-expression

TitleCigarette smoke induces growth differentiation factor 15 production in human lung epithelial cells: implication in mucin over-expression
Publication TypeJournal Article
Year of Publication2012
AuthorsWu Q, Jiang D, Chu HWei
JournalInnate Immun
Volume18
Issue4
Pagination617-26
Date Published2012 Aug
ISSN1753-4267
KeywordsCells, Cultured, Epithelial Cells, Gene Expression Regulation, Growth Differentiation Factor 15, Humans, Immunity, Mucosal, Lung, Mucin 5AC, Phosphatidylinositol 3-Kinases, Pulmonary Disease, Chronic Obstructive, Signal Transduction, Smoking, Transforming Growth Factor beta
Abstract

Excessive mucus is a hallmark of chronic obstructive pulmonary disease (COPD). There is an emerging interest in the role of TGF-β signaling in the initiation and progression of COPD. Growth differentiation factor 15 (GDF15) is a divergent member of TGF-β superfamily. However, whether cigarette smoke induces airway epithelial GDF15 production and its functions in the airways have not been revealed. Therefore, we first analyzed GDF15 protein expression in airway epithelium of human COPD smokers versus normal non-smokers. We then examined the regulation and function of GDF15 in human airway epithelial cells in response to cigarette smoke exposure. We found increased GDF15 protein expression in airway epithelium (mainly in ciliated cells) of human COPD smokers compared with normal non-smokers. Furthermore, cigarette smoke exposure consistently up-regulated GDF15 expression in human airway epithelial cells. Moreover, GDF15 was shown to play a critical role in cigarette smoke-induced airway epithelial MUC5AC expression. Lastly, activation of phosphoinositide 3-kinase (PI3K) pathway was largely responsible for GDF15-induced airway epithelial MUC5AC expression. Our findings indicate that human airway epithelial cells can produce GDF15 during cigarette smoke exposure, which subsequently activates PI3K pathway to promote mucin (e.g. MUC5AC) expression. This highlights a novel role of GDF15 in regulating airway mucosal immunity (e.g. mucin) in cigarette smoke-exposed lungs.

DOI10.1177/1753425911429837
Alternate JournalInnate Immun
PubMed ID22180562