Effects and clinical significance of NLRP3 inflammasome activated by IL-17A in CRSwNP.
10.3760/cma.j.cn115330-20220922-00576
- VernacularTitle:IL-17A激活NLRP3炎性小体在CRSwNP中的作用及临床意义
- Author:
Yue LI
1
;
Ya Na ZHANG
1
;
Li Hong CHANG
1
;
Wei Qiang HUANG
1
;
Hao Tian WU
1
;
Xi Fu WU
1
;
Zi Zhen HUANG
1
;
Ge Hua ZHANG
1
Author Information
1. Department of Otorhinolaryngology Head and Neck Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
- Publication Type:Journal Article
- MeSH:
Female;
Humans;
Male;
Chronic Disease;
Clinical Relevance;
Inflammasomes;
Interleukin-17/metabolism*;
Interleukin-18;
Nasal Polyps/metabolism*;
NLR Family, Pyrin Domain-Containing 3 Protein;
Rhinitis/metabolism*;
Sinusitis/metabolism*;
Young Adult;
Adult;
Middle Aged;
Aged
- From:
Chinese Journal of Otorhinolaryngology Head and Neck Surgery
2023;58(7):690-698
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the effects and clinical significance of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activated by interleukin (IL)-17A in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: Patients underwent nasal endoscopic surgery in the Third Affiliated Hospital of Sun Yat-sen University from January 2020 to December 2021 were collected, including 28 CRSwNP (including 19 males and 9 females, aged 19 to 67 years), 22 chronic rhinosinusitis without nasal polyps (CRSsNP) and 22 controls. qRT-PCR was used to detect the expressions of IL-17A, NLRP3, IL-1β and IL-18 in the three groups, and their correlations were analyzed. The positions of IL-17A, NLRP3 and IL-18 in nasal polys were analyzed by immunofluorescence. Western Blotting and ELISA were employed to detect the expression of NLRP3, IL-1β and IL-18 in the human nasal epithelial cells after using IL-17A stimulation or IL-17A receptor inhibitor. Immunofluorescence was used to observe the NLRP3, IL-1β, and IL-18 protein expression after IL-17A stimulating human nasal epithelial cells, and after the use of IL-17A receptor inhibitor and NLRP3 inhibitor MCC950. The correlations between NLRP3, IL-1β, IL-18 and CT scores, nasal endoscopic scores, visual analogue scale (VAS) scores, and sino-nasal outcome test (SNOT) 22 scores of CRSwNP patients were analyzed. SPSS 20.0 software was used for statistical analysis. Results: The expressions of IL-17A, NLRP3, IL-1β and IL-18 in the tissues of CRSwNP patients were significantly higher than those in CRSsNP group(P=0.018,P<0.001,P=0.005, P=0.016) and the control group(all P<0.001). IL-17A was positively correlated with the expression of NLRP3, IL-1β, and IL-18(r ralue was 0.643,0.650,0.629,respectively, all P<0.05). IL-17A, NLRP3, and IL-18 were co-localized in the epithelial propria of polyp tissue. IL-17A stimulated the expressions of NLRP3, IL-1β, and IL-18 in human nasal epithelial cells. After the use of IL-17A receptor inhibitor, the expressions of NLRP3, IL-1β, and IL-18 were significantly down-regulated. After the use of NLRP3 inhibitor MCC950, IL-17A was significantly down-regulated to promote the expression of NLRP3, IL-1β, and IL-18. The expressions of NLRP3, IL-1β and IL-18 were positively correlated with CT, nasal endoscopy, VAS, and SNOT22 scores in patients with CRSwNP. Conclusions: IL-17A promotes the release of IL-1β and IL-18 by activating the NLRP3 inflammasome and aggravates the severity of the disease in CRSwNP.
