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NLRP3炎症小体活化促进上皮细胞焦亡诱导变应性鼻炎 被引量:11

NLRP3 inflammasome activation promotes the development of allergic rhinitis via epithelium pyroptosis
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摘要 目的研究NLRP3炎症小体激活在变异性鼻炎的发生发展中的作用,并试图探讨其潜在的机制。方法利用野生型(wide-type,WT)和NLRP3基因敲除(knock out,KO)小鼠构建卵清蛋白(ovalbumin,OVA)诱导的变异性鼻炎模型。按照体质量将小鼠随机分为4组:WT、WT-OVA、NLRP3 KO、NLRP3 KO-OVA。观察小鼠的一般情况,用酶联免疫吸附测定白细胞介素1β(interleukin-1β,IL-1β);采用蛋白免疫印迹法检测NLRP3、GSDMD和Caspase-1 p20蛋白水平。结果WT-OVA组出现典型的变异性鼻炎症状,而敲除NLRP3炎症小体基因后可以显著改善OVA诱导的变异性鼻炎症状。与WT组相比,WT-OVA组IL-1β的表达上升,而NLRP3 KO-OVA组与WT-OVA组相比,IL-1β的表达明显下调,且差异均有统计学意义(均P<0.01)。与WT组相比,WT-OVA组NLRP3、GSDMD和Caspase-1 p20蛋白显著上调,而NLRP3 KO-OVA组与WT-OVA组相比,GSDMD和Caspase-1 p20蛋白表达明显下调,且差异均有统计学意义(均P<0.01)。结论NLRP3炎症小体通过增强炎症反应和上皮细胞焦亡来促进变异性鼻炎的发生发展,为探讨变异性鼻炎的发生机制及治疗提供新思路。 This study was designed to investigate the roles of NLRP3 inflammasome activation in the development and progression of allergic rhinitis(AR)and try to uncover its potential mechanisms.Wide-type(WT)and NLRP3 knock out(KO)mice were recruited to established AR disease model with ovalbumin(OVA)as the allergen.Mice were randomly divided into 4 groups,including WT,WT-OVA,NLRP3 KO and NLRP3 KO-OVA groups.Enzyme-linked immunosorbent(ELISA)was used to determine the level of interleukin-1β(IL-1β),while Western blot was used to detect the expression levels of NLRP3,GSDMD and Caspase-1 p20.The typical AR symptoms were found in WT-OVA group,and the knockdown of NLRP3 inflamosome gene significantly alleviated the symptoms of OVA-induced AR.Compared with WT group,the expression of IL-1βin the WT-OVA group was increased;and the expression of IL-1βin the NLRP3 KO-OVA group was significantly decreased compared with the WT-OVA group(all P<0.01).Compared with the WT group,the expressions of NLRP3,GSDMD and caspase-1 p20 were significantly up-regulated in the WT-OVA group;and significantly down-regulated in the NLRP3 KOOVA group compared with the WT-OVA group(all P<0.01).In conclusion,the NLRP3 inflammasome promotes the development and progression of AR via enhancing inflammatory response and epithelium pyroptosis,which provides a new way to explore the mechanism and treatment of AR.
作者 魏亚宁 仇惠莺 WEI Yaning;QIU Huiying(Department of Otolaryngology,Women and Children Hospital of Qinghai Province,Xining 810007,China)
出处 《免疫学杂志》 CAS CSCD 北大核心 2021年第2期140-144,共5页 Immunological Journal
关键词 变异性鼻炎 NLRP3炎症小体 焦亡 Allergic rhinitis NLRP3 inflammasome Pyroptosis
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