Pro-inflammatory role of NLRP3 inflammasome in experimental sterile corneal inflammation

Pro-inflammatory role of NLRP3 inflammasome in experimental sterile corneal inflammation
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DOI:
10.1038/s41598-019-46116-9
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发表时间:
2019-07
期刊:
影响因子:
4.6
通讯作者:
Hiroaki Shimizu;T. Sakimoto;S. Yamagami
Hiroaki Shimizu;T. Sakimoto;S. Yamagami
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hiroaki Shimizu;T. Sakimoto;S. Yamagami

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在C57BL6和NLRP3KO(NLRP3−/−)小鼠中,我们研究了NLRP3家族炎性小体在脂多糖或碱烧伤致无菌角膜炎症中的作用。C57BL6小鼠在碱烧伤和内毒素治疗后,NLRP3炎症体相关分子表达上调。碱烧伤后,Nlrp3−/−小鼠角膜混浊程度明显低于C57BL6小鼠。在Nlrp3−/−小鼠中,内毒素治疗和碱烧伤后角膜基质中Gr-1免疫反应和基质金属蛋白酶-9mRNA的表达均显著降低。定量聚合酶链式反应和免疫组织化学结果显示,碱烧伤和脂多糖处理的Nlrp3−/−小鼠角膜基质中IL-1和MMP9的表达均下调。这些发现表明,NLRP3炎性小体通过将中性粒细胞招募到炎症部位,在角膜中具有促炎作用。
We evaluated the role of NLR family pyrin domain containing 3 (NLRP3) inflammasome in sterile corneal inflammation caused by lipopolysaccharide (LPS) or alkali burns in C57BL6 mice or NLRP3 KO (Nlrp3−/−) mice. Various molecules related to the NLRP3 inflammasome were upregulated in C57BL6 mice after both alkali burn injury and LPS treatment. After alkali burn injury, the corneal opacity grade was significantly reduced inNlrp3−/−mice compared with C57BL6 mice. InNlrp3−/−mice, Gr-1 immunoreactivity and MMP-9 mRNA expression in the corneal stroma were significantly reduced by both LPS treatment and alkali burn injury. Quantitative PCR and immunohistochemistry revealed that IL-1β and MMP-9 expression in the corneal stroma were down-regulated inNlrp3−/−mice with both alkali burn injury and LPS treatment. These findings suggest that the NLRP3 inflammasome has a pro-inflammatory effect in the cornea by recruiting neutrophils to sites of inflammation.