A protective effect of FAM13A in human bronchial epithelial cells upon exposure to cigarette smoke
Cellular and molecular mechanisms (English)Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory lung disease. The onset of COPD is influenced by both genetic and environmental factors, including cigarette smoke and air pollution. Family With Sequence Similarity 13 Member A (FAM13A) is one of the most strongly associated genes with COPD. How FAM13A contributes to COPD is unclear. Here, we studied the role of FAM13A in pro-inflammatory responses and barrier dysfunction in human bronchial epithelial cells.
Gene expression of FAM13A was assessed upon exposure to cigarette smoke extract (CSE) in 16HBE cells. To further investigate its function, FAM13A was overexpressed and 16HBE cells were subsequently exposed to CSE. After confirmation of the overexpression, CXCL8 secretion was measured with ELISA and epithelial barrier function was monitored with Electric Cell-Substrate Impedance Sensing (ECIS).
Upon exposure to 20% CSE, gene expression of FAM13A was significantly down-regulated by ~0.6 fold. In CSE-exposed cells, overexpression of FAM13A resulted in a trend towards reduced CXCL8 levels compared to the empty vector. 16HBE cells overexpressing FAM13A built up resistance significantly more rapidly compared to empty vector control.
The reduced secretion of CXCL8 upon FAM13A overexpression implies an anti-inflammatory role of FAM13A. Thus, lower FAM13A expression upon cigarette smoking may act to increase airway epithelial CXCL8 release and neutrophilic inflammation. The more rapid building up of resistance suggests that FAM13A may improve epithelial barrier function by the (re)constitution of epithelial junctions. Overall, our results show that FAM13A may protect the airway epithelium against environmental exposures.