S1PR2 is Important for Cigarette Smoke-induced Pyroptosis in Human Bronchial Epithelial Cells

Abstract

Chronic obstructive pulmonary disease and other respiratory inflammatory diseases are often associated with cigarette smoke exposure. However, the underlying molecular mechanism remains unclear. This study aimed to investigate the role of sphingosine-1-phosphate receptor 2 (S1PR2) in cigarette smoke extract (CSE)-induced inflammation and pyroptosis in human bronchial epithelial (HBE) cells. CSE was administered to HBE cells and inflammation and pyroptosis were assessed. The mRNA levels of S1PR2, NLRP3, IL-1β, and IL-18 in HBE cells were detected by quantitative RT-PCR. Secreted protein levels of IL-1β and IL-18 in the culture supernatants were detected using enzyme-linked immunosorbent assay. Western blotting was used to measure the levels of S1PR2 and pyroptosis-related proteins (NLRP3, ASC, caspase-1, GSDMD, IL-1β, and IL-18). Our study revealed an upregulated expression of S1PR2, NLRP3, ASC, caspase-1, GSDMD, IL-1β, and regulated IL-18 in HBE cells after CSE exposure. Genetic blockage of S1PR2 could reverse the increased expression of these proteins related to CSE-induced pyroptosis. Conversely, S1PR2 overexpression increased CSE-induced pyroptosis by upregulating the expression of NLRP3, ASC, caspase-1, GSDMD, IL-1β, and IL-18 in HBE cells. Our results revealed that a novel S1PR2 signaling pathway may be involved in the pathogenesis of CSE-induced inflammation and pyroptosis in HBE cells. Thus, S1PR2 inhibitors could be an effective treatment for cigarette smoke-induced airway inflammation and injury.