Release of IL‐1β and IL‐18 in human primary bronchial epithelial cells exposed to cigarette smoke is independent of NLRP3

Abstract

AbstractCigarette smoke (CS) is a major risk factor for chronic lung diseases and promotes activation of pattern recognition receptors in the bronchial epithelium. NOD‐like receptor family, pyrin domain‐containing 3 (NLRP3) is a pattern recognition receptor whose activation leads to caspase‐1 cleavage, maturation/release of IL‐1β and IL‐18, and eventually pyroptosis. Whether the NLRP3 inflammasome participates in CS‐induced inflammation in bronchial epithelial cells is still unclear. Herein, we evaluated the involvement of NLRP3 in CS‐induced inflammatory responses in human primary bronchial epithelial cells. To this purpose, human primary bronchial epithelial cells were stimulated with CS extracts (CSE) and lytic cell death, caspase activation (‐1, ‐8, ‐3/7), cytokine release (IL‐1β, IL‐18, and IL‐8), NLRP3, pro‐IL‐1β/pro‐IL‐18 mRNA, and protein expression were measured. The impact of inhibitors of NLRP3 (MCC950), caspases, and the effect of the antioxidant N‐acetyl cysteine were evaluated. We found that CSE increased pro‐IL‐1β expression and induced activation of caspase‐1 and release of IL‐1β and IL‐18. These events were independent of NLRP3 and we found that NLRP3 was not expressed. N‐acetyl cysteine reverted CSE‐induced caspase‐1 activation. Overall, our findings support that the bronchial epithelium may play a central role in the release of IL‐1 family cytokines independently of NLRP3 in the lungs of smokers.