Acetylsalicylic Acid Promotes Corneal Epithelium Migration by Regulating Neutrophil Extracellular Traps in Alkali Burn.
Acetylsalicylic Acid Promotes Corneal Epithelium Migration by Regulating Neutrophil Extracellular Traps in Alkali Burn.
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乙酰水杨酸通过调节碱烧伤中性粒细胞胞外陷阱促进角膜上皮迁移
DOI：
10.3389/fimmu.2020.551057
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发表时间：
2020
影响因子：
7.3
通讯作者：
Jin X
中科院分区：
文献类型：
--
作者：
Wan T;Zhang Y;Yuan K;Min J;Mou Y;Jin X
中性粒细胞是响应于碱烧伤而迁移到角膜中的第一个细胞，并且过度的中性粒细胞浸润与炎性损伤和较差的预后相关。为了了解碱烧伤后中性粒细胞介导的炎症机制，我们研究了碱激活的中性粒细胞对人角膜上皮细胞（HCEs）增殖和迁移的作用，以及乙酰水杨酸（阿萨）和地塞米松（DXM）对NETosis的影响。我们用氢氧化钠（NaOH）刺激人中性粒细胞，并观察到剂量和时间依赖性中性粒细胞胞外陷阱（NET）的形成。我们还观察到，阿萨，而不是DXM，显着抑制NaOH诱导的NETosis。此外，核因子（NF）-κB的激活，而不是活性氧的产生，参与ASA调节NETosis。此外，NET被发现参与碱激活的中性粒细胞（AN）诱导的嗜中性粒细胞-HCE粘附。ANs通过吞噬作用促进HCEs增殖。同时，ANs通过释放NETs抑制HCEs迁移，5 mM阿萨可部分挽救NETs。总之，ANs可能分别通过吞噬作用和NETs形成来干扰HCE的增殖和迁移。阿萨可能通过抑制NF-κB活化减少NETs的形成而促进HCEs迁移，可能是改善角膜碱烧伤预后的一种有前景的策略。
Neutrophils are the first cells to migrate into the cornea in response to alkali burns, and excessive neutrophil infiltration is associated with inflammatory injury and a poorer prognosis. In an effort to understand the mechanisms underlying the inflammation mediated by neutrophils after alkali burns, we examined the role of alkali-activated neutrophils on human corneal epithelial cells (HCEs) proliferation and migration, as well as the effects of acetylsalicylic acid (ASA) and dexamethasone (DXM) on NETosis. We stimulated human neutrophils with sodium hydroxide (NaOH) and observed dose- and time-dependent neutrophil extracellular traps (NETs) formation. We also observed that ASA, but not DXM, significantly inhibited NaOH-induced NETosis. Furthermore, the activation of nuclear factor (NF)-κB, but not the production of reactive oxygen species, was involved in ASA-regulated NETosis. Moreover, NETs were found to be involved in alkali-activated neutrophils (ANs) induced neutrophil-HCE adhesion. ANs enhanced HCEs proliferation via phagocytosis. Meanwhile, ANs inhibited HCEs migration through the release of NETs, which was partially rescued by 5 mM ASA. In conclusion, ANs may interfere with HCEs proliferation and migration by phagocytosis and NETs formation, respectively. ASA may enhance HCEs migration by decreasing NETs formation through inhibition of NF-κB activation and could be a promising strategy for improving the prognosis of corneal alkali burns.