Qidong People's Hospital, Qidong, China.
The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Inflammation. 2018 Feb;41(1):164-173. doi: 10.1007/s10753-017-0674-6.
The nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome has developed as an important bridge between innate immune and infection recently, and has the ability to drive proteolytic procaspase-1 into bioactive caspase-1, then responsible for proteolytic processing of inflammatory cytokines IL-1β and IL-18. Fungal β-glucan, a major component of fungal cell wall, triggers inflammatory response in multiple immune cells, but rarely described in epithelial cells. Also, the relationship between fungal β-glucan and NLRP3 inflammasome is not clear yet. In this study, we first identified that curdlan, a large particulate β-glucan, could activate the NLRP3 inflammasome in LPS-primed human bronchial epithelial cells (HBECs). RT-PCR and Western Blot showed that curdlan upregulate the mRNA as well as intracellular protein expression of NLRP3 and IL-1β in HBECs, along with the activity of caspase-1, and the level of mature IL-1β in cell supernatants was higher by ELISA detection. Further studies demonstrated that the activation of NLRP3 inflammasome could be attenuated by NAC, an inhibitor of ROS. Thus, it indicated curdlan activate NLRP3 inflammasome through a pathway requiring ROS production in HBECs. These findings may provide a new therapeutic target, NLRP3 inflammasome, in invasive pulmonary fungal infections.
核苷酸结合域和富含亮氨酸重复蛋白 3 (NLRP3) 炎性小体最近已成为先天免疫和感染之间的重要桥梁，具有将蛋白水解酶原 procaspase-1 转化为生物活性 caspase-1 的能力，进而负责炎性细胞因子 IL-1β 和 IL-18 的蛋白水解加工。真菌 β-葡聚糖是真菌细胞壁的主要成分，可在多种免疫细胞中引发炎症反应，但在上皮细胞中很少被描述。此外，真菌 β-葡聚糖与 NLRP3 炎性小体之间的关系尚不清楚。在本研究中，我们首先鉴定出，一种大型颗粒状β-葡聚糖，即昆布多糖，可在 LPS 预刺激的人支气管上皮细胞（HBECs）中激活 NLRP3 炎性小体。RT-PCR 和 Western Blot 显示，昆布多糖可上调 HBECs 中 NLRP3 和 IL-1β 的 mRNA 以及细胞内蛋白表达，同时还能激活 caspase-1，且通过 ELISA 检测到细胞上清液中成熟的 IL-1β 水平更高。进一步的研究表明，NLRP3 炎性小体的激活可被 NAC 减弱，NAC 是 ROS 的抑制剂。因此，这表明昆布多糖通过需要 ROS 产生的途径在 HBECs 中激活 NLRP3 炎性小体。这些发现可能为侵袭性肺部真菌感染提供一个新的治疗靶点，即 NLRP3 炎性小体。
