Wood smoke particulate matter (WSPM2.5) induces pyroptosis through both Caspase-1/IL-1β/IL-18 and ATP/P2Y-dependent mechanisms in human bronchial epithelial cells. (November 2022)

• Record Type: Journal Article
• Authors: Fu, Xin; Hong, Wei; Li, Shuyi; Chen, Zhi; Zhou, Wenqu; Dai, Jianwei; Deng, Xiaoliang; Zhou, Hongbin; Li, Bing; Ran, Pixin
• Is Part Of: Chemosphere. Volume 307:Part 2(2022)
• Publication Date: 2022-11
• Subjects: Particulate matter (PM2.5) -- Pyroptosis -- Caspase-1 -- Interleukin (IL-1β) -- Adenosine triphosphate (ATP) -- Bronchial epithelial cells; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2022.135726
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: Emerging evidences have linked the air pollution particulate matters, especially the fine particulate matter PM2.5, to the disease development of chronic obstructive pulmonary disease (COPD). Our previous studies reported that biofuel PM2.5 can induce devastated damage of human bronchial epithelial cells, this study aims to further investigate the underlying molecular mechanisms how biofuel PM2.5 induces bronchial epithelial cell death and dysfunction. In this study, biofuel PM2.5 extracted from wood smoke (WSPM2.5) was used according to our previous publication. A 16-HBE cell line was used as the cell model. Results showed that: Firstly, WSPM2.5 induced significant pyroptosis in 16-HBE cells, reflected by the typical changes including elevated release of lactate dehydrogenase release (LDH) and activated activity and expression of Caspase-1/IL-1β/IL-18 signaling pathway. Then, specific inhibitors for both Caspases (Z-VAD-FMK) and Caspase-1 (VX-765), as well as specific siRNA knockdown of IL-1β all effectively attenuated the WSPM2.5-induced upregulation of downstream inflammatory cytokines and chemokines (IL-6, IL-8, CXCL-1, CXCL-2, etc), respectively. Notably, WSPM2.5 caused a novel increase of intracellular-to-extracellular ATP secretion, which could also contribute to the WSPM2.5-induced pyroptosis and inflammation by activating the Caspase-1/IL-1β/IL-18 signaling pathway through possible autocrine and/or paracrine mechanisms. Antagonism of ATP (Apyrase) or specific siRNA knockdown against ATP receptors (P2Y2 and P2Y7) both significantly inhibited the WSPM2.5-induced pyroptosis and inflammation. These results add up to the current knowledge and bring up novel insights that WSPM2.5 could induce significant pyroptosis and inflammation of human bronchial epithelial cells, through both a classic NLRP3/Caspase-1/IL-1β-dependent and a novel ATP/P2Y-dependent mechanisms. Graphical abstract: Image 1 Highlights: Wood smoke PM2.5 (WSPM2.5) induces pyroptosis in human bronchial epithelial cells. WSPM2.5 induces pyroptosis through Caspase-1/IL-1β/IL-18 signaling pathway. WSPM2.5-induced ATP secretion drives pyroptosis through P2Y2/P2Y7-dependent mechanism.