International immunopharmacology · 2019
Celastrol ameliorates Aspergillus fumigatus keratitis via inhibiting LOX-1.
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Sun Qiaoqiao, Li Cui, Lin Jing, Peng Xudong, Wang Qian, Jiang Nan, Xu Qiang, Zhao Guiqiu
Аннотация
PURPOSE: To investigate the effect of Celastrol (CLT) on Aspergillus fumigatus (A. fumigatus) keratitis.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.