Lin Hai, Li Zhipeng, Lin Dong, Zheng Chunquan, Zhang Weitian
Department of Otorhinolaryngology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Department of Otorhinolaryngology, Fuzhou General Hospital, Fuzhou, 350025, Fujian, China.
Inflammation. 2016 Dec;39(6):2045-2052. doi: 10.1007/s10753-016-0442-z.
The pathophysiologic mechanisms of human chronic rhinosinusitis with nasal polyps (CRSwNP) remain unclear. We aimed to elucidate expression and biologic role of NLRP3 inflammasome in CRSwNP. Immunohistochemistry (IHC) was conducted to assess NLRP3 immunolabeling, real-time polymerase chain reaction (PCR) was used for IL-9 and NLRP3, and caspase-1 level quantitation in CRSwNP and control subjects. In addition, enzyme-linked immunosorbent assay (ELISA) was employed for analyzing concentrations of IL-1β and IL-18 in the homogenates prepared from tissue specimens. Moreover, human nasal epithelial cells (HNECs) were used to evaluate the effects of lipopolysaccharide (LPS) and glyburide on NLRP3 inflammasome signaling pathway. Results showed that NLRP3 and caspase-1 were overexpressed in CRSwNP, especially in eosinophilic CRSwNP (ECRSwNP). Interestingly, NLRP3 expression had close correlation to that of caspase-1. Concentrations of IL-1β and IL-18 were elevated. NLRP3 inflammasome signaling pathway was augmented by LPS but suppressed by glyburide. In conclusion, NLRP3 inflammasome signaling pathway played a pro-inflammatory role in the pathogenesis of CRSwNP, especially in ECRSwNP. NLRP3 inflammasome signaling pathway was augmented by LPS, but suppressed by glyburide.
伴有鼻息肉的人类慢性鼻-鼻窦炎（CRSwNP）的病理生理机制仍不清楚。我们旨在阐明NLRP3炎性小体在CRSwNP中的表达及生物学作用。采用免疫组织化学（IHC）评估NLRP3免疫标记，运用实时聚合酶链反应（PCR）检测CRSwNP患者和对照者中白细胞介素-9（IL-9）、NLRP3及胱天蛋白酶-1水平。此外，采用酶联免疫吸附测定（ELISA）分析组织标本匀浆中IL-1β和IL-18的浓度。而且，利用人鼻上皮细胞（HNECs）评估脂多糖（LPS）和格列本脲对NLRP3炎性小体信号通路的影响。结果显示，NLRP3和胱天蛋白酶-1在CRSwNP中过度表达，尤其是在嗜酸性粒细胞性CRSwNP（ECRSwNP）中。有趣的是，NLRP3表达与胱天蛋白酶-1的表达密切相关。IL-1β和IL-18浓度升高。LPS增强NLRP3炎性小体信号通路，而格列本脲抑制该通路。总之，NLRP3炎性小体信号通路在CRSwNP发病机制中发挥促炎作用，尤其是在ECRSwNP中。LPS增强NLRP3炎性小体信号通路，而格列本脲抑制该通路。
