Celastrol ameliorates Aspergillus fumigatus keratitis via inhibiting LOX-1

Celastrol ameliorates Aspergillus fumigatus keratitis via inhibiting LOX-1
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雷公藤红素通过抑制 LOX-1 改善烟曲霉角膜炎

DOI:
10.1016/j.intimp.2019.02.017
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发表时间:
2019
影响因子:
5.6
通讯作者:
Guiqiu Zhao
Guiqiu Zhao
中科院分区:
医学2区
文献类型:
--
作者:
Qiaoqiao Sun;Cui Li;Jing Lin;Xudong Peng;Qian Wang;Nan Jiang;Qiang Xu;Guiqiu Zhao

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目的探讨雷公藤红素(CLT)对烟曲霉(Aspergillusfumigatus)角膜炎的影响。熏蒸刺激物。C57BL/6小鼠感染A。烟雾剂。小鼠角膜在感染 后1天开始接受CLT治疗。采用临床评分、聚合酶链式反应、酶联免疫吸附试验和免疫印迹等方法检测抗炎介质、促炎介质和凝集素样氧化型低密度脂蛋白受体1(LOX-1)的表达。C57BL/6小鼠经CLT处理后,巨噬细胞中p38MAPK的蛋白表达水平明显下降。结果C57BL/6小鼠在感染 后1天开始接受CLT治疗后,病情明显减轻,IL-1β、肿瘤坏死因子α、IL-10、转化生长因子β、MIP-2和LOX-1水平明显降低。与对照组相比,CLT明显抑制C57BL/6小鼠巨噬细胞抗炎介质、促炎介质和LOX-1的mRNA和蛋白水平。CLT前的预处理。与DMSO预处理组相比,烟熏刺激可明显抑制经a攻击的C57BL/6小鼠巨噬细胞中p38MAPK的蛋白表达。结论这些数据提供了CLT改善A。通过抑制LOX-1抑制C57BL/6小鼠烟熏角膜炎。CLT前的预处理。烟熏刺激可降低C57BL/6小鼠巨噬细胞的炎症水平,其作用可能受p-p38MAPK的调节。
PurposeTo investigate the effect of Celastrol (CLT) on Aspergillus fumigatus (A. fumigatus) keratitis.MethodsPrimary peritoneal macrophages of C57BL/6 mice were pretreated with CLT beforeA. fumigatushyphae stimulation. C57BL/6 mice were infected withA. fumigatus. Mice corneas were treated with CLT from 1 day post infection. Clinical score, PCR, ELISA and Western blot were used to test expression of anti-inflammatory mediators, proinflammatory mediators and Lectin-like oxidized low-density lipoprotein receptor 1(LOX-1). The protein levels of p38MAPK after pretreated with CLT in macrophages of C57BL/6 mice challenged withA. fumigatuswere tested by Western blot.ResultsC57BL/6 mice treated with CLT from 1 day post infection showed decreased disease, IL-1β, TNF-α, IL-10, TGF-β, MIP-2 and LOX-1 levels. CLT treatment markedly inhibiting mRNA and proteins levels of anti-inflammatory mediators, proinflammatory mediators and LOX-1 in macrophages of C57BL/6 mice compared with control group. CLT pretreatment beforeA. fumigatusstimulation obviously inhibiting protein levels of p38MAPK versus DMSO pretreated group in macrophages of C57BL/6 mice challenged withA. fumigatus.ConclusionThese data provide evidences that CLT amelioratesA. fumigatuskeratitis of C57BL/6 mice via inhibiting LOX-1. CLT pretreatment beforeA. fumigatusstimulation decreased levels of inflammation in macrophages of C57BL/6 mice, which may be regulated by p-p38MAPK.