Wood smoke particulate matter (WSPM2.5) induces pyroptosis through both Caspase-1/IL-10/IL-18 and ATP/P2Y-dependent mechanisms in human bronchial epithelial cells
Wood smoke particulate matter (WSPM2.5) induces pyroptosis through both Caspase-1/IL-10/IL-18 and ATP/P2Y-dependent mechanisms in human bronchial epithelial cells
复制标题
DOI：
10.1016/j.chemosphere.2022.135726
复制
发表时间：
2022-08-02
期刊：
影响因子：
8.8
通讯作者：
Ran, Pixin
中科院分区：
文献类型：
--
作者：
Fu, Xin;Hong, Wei;Ran, Pixin
越来越多的证据表明，空气污染颗粒物，尤其是细颗粒物 PM2.5，与慢性阻塞性肺病 (COPD) 的疾病发展有关。我们前期的研究报道生物燃料PM2.5可引起人支气管上皮细胞的严重损伤，本研究旨在进一步探讨生物燃料PM2.5诱导支气管上皮细胞死亡和功能障碍的分子机制。在本研究中，根据我们之前的出版物，使用从木烟中提取的生物燃料 PM2.5 (WSPM2.5)。使用 16-HBE 细胞系作为细胞模型。结果表明：首先，WSPM2.5诱导16-HBE细胞发生显着的细胞焦亡，其典型变化包括乳酸脱氢酶释放（LDH）释放增加以及Caspase-1/IL-10/IL-18信号通路活性和表达激活。然后，Caspase (Z-VAD-FMK) 和 Caspase-1 (VX-765) 的特异性抑制剂以及 IL-10 的特异性 siRNA 敲低均有效地分别减弱了 WSPM2.5 诱导的下游炎症细胞因子和趋化因子（IL-6、IL-8、CXCL-1、CXCL-2 等）的上调。值得注意的是，WSPM2.5 引起细胞内到细胞外 ATP 分泌的新增加，这也可能通过可能的自分泌和/或旁分泌机制激活 Caspase-1/IL-1 beta/IL-18 信号通路，从而导致 WSPM2.5 诱导的细胞焦亡和炎症。 ATP (Apyrase) 拮抗作用或针对 ATP 受体（P2Y2 和 P2Y7）的特异性 siRNA 敲低均能显着抑制 WSPM2.5 诱导的细胞焦亡和炎症。这些结果补充了当前的知识，并提出了新的见解，即 WSPM2.5 可以通过经典的 NLRP3/Caspase-1/IL-1 beta 依赖性和新的 ATP/P2Y 依赖性机制诱导人支气管上皮细胞显着焦亡和炎症。
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 re-ported 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-10/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-10 all effectively attenuated the WSPM2.5-induced upregulation of downstream in-flammatory 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-1 beta/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-1 beta-dependent and a novel ATP/P2Y-dependent mechanisms.