CKLF1/CCR5 axis is involved in neutrophils migration of rats with transient cerebral ischemia
CKLF1/CCR5 axis is involved in neutrophils migration of rats with transient cerebral ischemia
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CKLF1/CCR5轴参与短暂性脑缺血大鼠中性粒细胞迁移
DOI：
10.1016/j.intimp.2020.106577
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发表时间：
2020-08-01
影响因子：
5.6
通讯作者：
Chen, Nai-hong
中科院分区：
文献类型：
--
作者：
Chen, Chen;Chu, Shi-feng;Chen, Nai-hong
背景：趋化因子样因子1（CKLF 1）是一种在脑卒中后缺血性脑组织中显著升高的趋化因子。它显示了对各种免疫细胞的趋化作用，但CKLF 1迁移中性粒细胞的机制知之甚少。最近的研究提供了证据表明，CC趋化因子受体5（CCR 5），CKLF 1的受体，参与缺血性卒中。目的：研究HIF-1 α引导的AAV在缺血性脑中的作用，研究卒中的结局，并检查CKLF 1/CCR 5轴参与中性粒细胞的募集。HIF-1 α介导的AAV在脑缺血区下调CKLF 1表达，减轻脑损伤。CKLF 1通过CCR 5迁移中性粒细胞，恶化炎症反应。Akt/GSK-3 β通路可能参与CKLF 1/CCR 5轴介导的中性粒细胞趋化。结论：CKLF 1/CCR 5轴参与了短暂性脑缺血大鼠中性粒细胞的迁移。CKLF 1/CCR 5轴可能是脑卒中治疗的一个有用靶点。
Background: Chemokine-like factor 1 (CKLF1) is a chemokine increased significantly in ischemic brain post-stroke. It shows chemotaxis effects on various immune cells, but the mechanisms of CKLF1 migrating neutrophils are poorly understood. Recent studies have provided evidence that CC chemokine receptor 5 (CCR5), a receptor of CKLF1, is involved in ischemic stroke.Purposes: To investigate the effects of HIF-1 alpha guided AAV in ischemic brain, investigating the outcome of stroke, and examining the involvement of CKLF1/CCR5 axis in recruitment of neutrophils.Results: HIF-1 alpha guided AAV knocked down CKLF1 in ischemic area and alleviated brain damage of rats. CKLF1 migrated neutrophils through CCR5, worsening inflammatory responses. Akt/GSK-3 beta pathway may involve in CKLF1/CCR5 axis guided neutrophils chemotaxis.Conclusions: CKLF1/CCR5 axis is involved in neutrophils migration of rats with transient cerebral ischemia. CKLF1/CCR5 axis may be a useful target for stroke therapy.