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

Abstract

BACKGROUND:

Chronic obstructive pulmonary disease and other respiratory inflammatory diseases are often associated with cigarette smoke exposure. However, the underlying molecular mechanism remains unclear.

AIM OF THE STUDY:

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.

METHODS:

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).

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Huan Xu, Feng Xu, Hongyu Lu, Jiexin Chen, Xiaoling Huang, Yongsong Chen, Ling Lin
• Journal: Archives of medical research (Arch Med Res) Vol. 54 Issue 4 Pg. 277-286 (06 2023) ISSN: 1873-5487 [Electronic] United States
• PMID: 36990889 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023. Published by Elsevier Inc.

Chemical References

• Interleukin-18
• NLR Family, Pyrin Domain-Containing 3 Protein
• Sphingosine-1-Phosphate Receptors
• Caspases
• S1PR2 protein, human

Topics

• Humans
• Pyroptosis
• Interleukin-18 (metabolism, pharmacology)
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Cigarette Smoking
• Sphingosine-1-Phosphate Receptors (metabolism)
• Epithelial Cells
• Inflammation (pathology)
• Caspases (metabolism)