Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
Int Immunopharmacol. 2019 May;70:101-109. doi: 10.1016/j.intimp.2019.02.017. Epub 2019 Feb 21.
To investigate the effect of Celastrol (CLT) on Aspergillus fumigatus (A. fumigatus) keratitis.
Primary peritoneal macrophages of C57BL/6 mice were pretreated with CLT before A. fumigatus hyphae stimulation. C57BL/6 mice were infected with A. 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 with A. fumigatus were tested by Western blot.
C57BL/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 before A. fumigatus stimulation obviously inhibiting protein levels of p38MAPK versus DMSO pretreated group in macrophages of C57BL/6 mice challenged with A. fumigatus.
These data provide evidences that CLT ameliorates A. fumigatus keratitis of C57BL/6 mice via inhibiting LOX-1. CLT pretreatment before A. fumigatus stimulation decreased levels of inflammation in macrophages of C57BL/6 mice, which may be regulated by p-p38MAPK.
研究塞拉托司（CLT）对烟曲霉（A. fumigatus）角膜炎的作用。
在烟曲霉菌丝刺激前，用 CLT 预处理 C57BL/6 小鼠的原代腹腔巨噬细胞。用 A. fumigatus 感染 C57BL/6 小鼠。从感染后 1 天开始，用 CLT 处理小鼠角膜。采用临床评分、PCR、ELISA 和 Western blot 检测抗炎介质、促炎介质和凝集素样氧化低密度脂蛋白受体 1（LOX-1）的表达。用 Western blot 检测 A. fumigatus 刺激后用 CLT 预处理的 C57BL/6 小鼠巨噬细胞中 p38MAPK 的蛋白水平。
感染后 1 天开始用 CLT 处理的 C57BL/6 小鼠，疾病、IL-1β、TNF-α、IL-10、TGF-β、MIP-2 和 LOX-1 水平降低。与对照组相比，CLT 处理明显抑制 C57BL/6 小鼠巨噬细胞中抗炎介质、促炎介质和 LOX-1 的 mRNA 和蛋白水平。与 DMSO 预处理组相比，A. fumigatus 刺激前用 CLT 预处理明显抑制 A. fumigatus 刺激后 C57BL/6 小鼠巨噬细胞中 p38MAPK 的蛋白水平。
这些数据提供了证据，表明 CLT 通过抑制 LOX-1 改善 C57BL/6 小鼠的烟曲霉角膜炎。A. fumigatus 刺激前用 CLT 预处理降低了 C57BL/6 小鼠巨噬细胞中的炎症水平，这可能是由 p-p38MAPK 调节的。
