Hypoxia regulated NLRP3 inflammmasome mediated neutrophilicinflammation by promoting oxidase stress in nasal mucosa
Saturday, March 3, 2018
South Hall A2 (Convention Center)
Yi Wei, Liman Liu, Xingliang Fan
RATIONALE: Inflammasome is a platform of caspase activation that mediated innate immunity, which is found to be involved in the pathogenesis of several inflammatory diseases such as diabetes and atherosclerosis, etc. However, the possible role of inflammasome in the formation of nasal polyps has largely been unknown.

METHODS: Nasal tissue samples were collected from 57 CRSwNP patients and 32 control subjects. CRSwNP patients were divided into neutrophilia and non- neutrophilia subtypes based on immunohistochimical staining of Neutrophil elastase (NEU). The expression of NLRP3 and inflammasome mRNA were examined using real-time PCR, and protein were measured using immunoblot and immunohistochemical and immunofluorescence staining. The mRNA levels of IL-1α, IL-18 in polyp tissues were analyzed by real-time RT-PCR. Moreover, the expression of IL-1α in dispersed NP cells after ATP or hypoxia stimulation was measured using real-time RT-PCR and ELISA.

RESULTS: NLRP3 (inculding other components of inflammasome) and its-derived IL-1β were upregulated in nasal mucosa and CD68 positive macrophage. Tissue hypoxia activated NLRP3 inflammasome may contribute to the characteristical tissue neutrophilia in Chinese patients with nasal polyps.

CONCLUSIONS: Inflammasome may be involved in the pathophysiology of nasal polyps.Our previous finding that Chinese patients with nasal polyps possessed characteristical tissue neutrophilia, and the well-recognized fact that NLRP3 inflammasome-derived IL-1β plays a critical role in neutrophil chemostaxis and activation.This study may elucidate a molecular mechanism underlying the pathogenesis of Chinese patients with nasal polyps by detecting how hypoxia promotes oxidase stress and regulates the activation of NLRP3 inflammasome, and establish an effective strategy for the treatment of nasal polyps.