[1]董训虎,陈明亮,余文珮,等.维生素D3通过抑制NLRP3炎性小体激活改善氮芥诱导角质形成细胞炎性损伤[J].第三军医大学学报,2020,42(03):267-272.
 DONG Xunhu,CHEN Mingliang,YU Wenpei,et al.Vitamin D3 ameliorates nitrogen mustard-induced keratinocytes inflammation by inactivating NLRP3 inflammasome activation[J].J Third Mil Med Univ,2020,42(03):267-272.
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维生素D3通过抑制NLRP3炎性小体激活改善氮芥诱导角质形成细胞炎性损伤(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
42卷
期数:
2020年第03期
页码:
267-272
栏目:
基础医学
出版日期:
2020-02-15

文章信息/Info

Title:
Vitamin D3 ameliorates nitrogen mustard-induced keratinocytes inflammation by inactivating NLRP3 inflammasome activation
作者:
董训虎陈明亮余文珮叶枫但国蓉邹仲敏
陆军军医大学(第三军医大学)军事预防医学系防化医学教研室
Author(s):
DONG Xunhu CHEN Mingliang YU Wenpei YE Feng DAN Guorong ZOU Zhongmin

Department of Chemical Defense, Faculty of Military Preventive Medicine, Army Medical University (Third Military Medical University),  Chongqing, 400038, China

关键词:
氮芥维生素D3NLRP炎性小体角质形成细胞炎性反应
Keywords:
 
分类号:
R827.174; R967; R977.24
文献标志码:
A
摘要:

目的 探讨NLRP3炎性小体在维生素D3(vitamin D3,VD3)改善氮芥(nitrogen mustard, NM)诱导角质形成细胞炎性损伤中的作用和机制。方法用20 μmol/L NM单独或联合用10 μmol/L caspase-1特异抑制剂(Ac-YVAD-cmk , YVAD)、10 μmol/L NLRP3炎性小体特异抑制剂(MCC950)、5 nmol/L VD3处理人角质形成细胞株(HaCaT细胞)4 h。应用CCK-8法检测细胞增殖活力,Western blot检测NLRP3、caspase-1 p20、IL-1β和COX-2的表达水平,ELISA检测IL-1β释放量。结果20 μmol/L NM对HaCaT细胞增殖活力无显著影响,NM处理后可显著上调HaCaT细胞NLRP3、caspase-1 p20、IL-1β和COX-2的蛋白表达水平,增加细胞IL-1β释放(P<0.05)。而加入MCC950或YVAD处理后能显著抑制NM诱导的上述效应(P<0.05);同时,VD3干预能够明显抑制NM对NLRP3和caspase-1 p20蛋白表达的上调作用,并显著减少NM诱导的IL-1β和COX-2的表达和释放(P<0.05)。结论VD3通过抑制NLRP3炎性小体激活减少角质形成细胞炎性因子生成,改善NM诱导的细胞炎性损伤。

Abstract:

Objective To investigate the effect of vitamin D3 on nitrogen mustard (NM)-induced keratinocyte inflammation and the role of NOD-like receptor protein 3 (NLRP3) inflammasome in the process. MethodsHaCaT cells were treated with 20 μmol/L NM, in the presence or absence of 10 μmol/L MCC950 (a specific inhibitor of NLRP3 inflammasome) or 10 μmol/L Ac-YVAD-cmk (YVAD, a specific activator of caspase-1) or 5 nmol/L vitamin D3 for 4 h. CCK-8 assay was used to detect cell viability. The IL-1β content in the supernatant of cell lysate was determined by Human IL-1β ELISA kit, and the expression of NLRP3, caspase-1, IL-1β and COX-2 was detected by Western blotting. ResultsTreatment with 20 μmol/L NM had no significant effect on the viability of HaCaT cells, but remarkably up-regulated the expression of NLRP3, caspase-1 p20, IL-1β and COX-2, and enhanced the accumulation of IL-1β in the culture supernatant of HaCaT cells (P<0.05). Moreover, MCC950 or YVAD treatment abolished the above effects of NM (P<0.05). Simultaneously, vitamin D3 treatment notably inhibited the upregulated expression of NLRP3 and caspase-1 p20, and remarkably reduced the increased expression and release of IL-1β and COX-2 in HaCaT cells induced by NM (P<0.05). ConclusionVitamin D3 ameliorates NM-induced keratinocytes inflammation by reducing the synthesis of inflammatory mediators through suppressing the activation of NLRP3 inflammasome.

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更新日期/Last Update: 2020-02-06