%0 Journal Article %T Release of IL-1β and IL-18 in human primary bronchial epithelial cells exposed to cigarette smoke is independent of NLRP3. %A Dino P %A Giuffrè MR %A Buscetta M %A Di Vincenzo S %A La Mensa A %A Cristaldi M %A Bucchieri F %A Lo Iacono G %A Bertani A %A Pace E %A Cipollina C %J Eur J Immunol %V 0 %N 0 %D 2024 Jul 27 %M 39072707 %F 6.688 %R 10.1002/eji.202451053 %X Cigarette 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.