Neutralization of chemokine-like factor 1, a novel C-C chemokine, protects against focal cerebral ischemia by inhibiting neutrophil infiltration via MAPK pathways in rats.
Neutralization of chemokine-like factor 1, a novel C-C chemokine, protects against focal cerebral ischemia by inhibiting neutrophil infiltration via MAPK pathways in rats.
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趋化因子样因子 1（一种新型 C-C 趋化因子）的中和作用可通过 MAPK 途径抑制中性粒细胞浸润，从而预防局灶性脑缺血
DOI：
10.1186/1742-2094-11-112
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发表时间：
2014-06-20
影响因子：
9.3
通讯作者：
Chen NH
中科院分区：
文献类型：
--
作者：
Kong LL;Wang ZY;Han N;Zhuang XM;Wang ZZ;Li H;Chen NH
研究背景炎症在缺血性脑卒中的病理生理过程中起着关键作用。一些促炎介质，如细胞因子和趋化因子，在中风中产生。趋化因子样因子1（CKLF 1）作为一种新型的C-C趋化因子，在广泛的白细胞中具有趋化活性，在脑发育中起重要作用。在以前的研究中，我们发现大鼠局灶性脑缺血后CKLF 1的表达增加，并且用CKLF 1拮抗剂C19肽治疗可减少梗死面积和含水量。然而，CKLF 1在脑卒中中的作用仍不清楚。本研究的目的是确定CKLF 1在缺血性脑损伤中可能的作用和机制，通过应用抗CKLF 1 antibody.MethodsMale Sprague-Dawley大鼠大脑中动脉闭塞1小时。再灌注后立即将CKLF 1抗体应用于右脑室;在脑缺血后24和72小时测量梗死体积和神经功能评分。采用RT-PCR、Western blotting和ELISA方法检测细胞粘附分子、炎症因子和MAPK信号通路的表达。免疫组织化学染色和髓过氧化物酶活性被用来确定中性粒细胞infiltration.ResultsTreatment的程度与抗CKLF 1抗体显着降低神经评分和梗死体积的剂量依赖性的方式在脑缺血后24和72小时。抗CKLF 1抗体可降低炎症因子TNF-α、IL-1β、MIP-2和IL-8的水平及粘附分子ICAM-1和VCAM-1的表达，并呈剂量依赖性。免疫组化染色和MPO活性检测结果表明，抗CKLF 1抗体可抑制中性粒细胞浸润。结论CKLF 1可能成为脑缺血治疗的新靶点。
BackgroundInflammation plays a key role in the pathophysiology of ischemic stroke. Some proinflammatory mediators, such as cytokines and chemokines, are produced in stroke. Chemokine-like factor 1 (CKLF1), as a novel C-C chemokine, displays chemotactic activities in a wide spectrum of leukocytes and plays an important role in brain development. In previous studies, we have found that the expression of CKLF1 increased in rats after focal cerebral ischemia and treatment with the CKLF1 antagonist C19 peptide decreased the infarct size and water content. However, the role of CKLF1 in stroke is still unclear. The objective of the present study was to ascertain the possible roles and mechanism of CKLF1 in ischemic brain injury by applying anti-CKLF1 antibody.MethodsMale Sprague–Dawley rats were subjected to one-hour middle cerebral artery occlusion. Antibody to CKLF1 was applied to the right cerebral ventricle immediately after reperfusion; infarct volume and neurological score were measured at 24 and 72 hours after cerebral ischemia. RT-PCR, Western blotting and ELISA were utilized to characterize the expression of adhesion molecules, inflammatory factors and MAPK signal pathways. Immunohistochemical staining and myeloperoxidase activity was used to determine the extent of neutrophil infiltration.ResultsTreatment with anti-CKLF1 antibody significantly decreased neurological score and infarct volume in a dose-dependent manner at 24 and 72 hours after cerebral ischemia. Administration with anti-CKLF1 antibody lowered the level of inflammatory factors TNF-α, IL-1β, MIP-2 and IL-8, the expression of adhesion molecules ICAM-1 and VCAM-1 in a dose-dependent manner. The results of immunohistochemical staining and detection of MPO activity indicated that anti-CKLF1 antibody inhibited neutrophil infiltration. Further studies suggested MAPK pathways associated with neutrophil infiltration in cerebral ischemia.Conclusions Therefore, CKLF1 may be a novel target for the treatment of stroke.
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DOI：
10.1016/j.bbapap.2005.08.017
发表时间：
2005-12-30
影响因子：
3.2
作者：
Kaminska, B
通讯作者：
Kaminska, B
影响因子：
4.8
作者：
Kanemoto, Y;Nakase, H;Sakaki, T
通讯作者：
Sakaki, T
CXCR4 拮抗剂 AMD3100 保护小鼠血脑屏障完整性并减少局灶性缺血后的炎症反应
影响因子：
8.3
作者：
Huang, Jun;Li, Yaning;Wang, Yongting
通讯作者：
Wang, Yongting
C19 是趋化因子样因子 1 的 C 端肽，可保护大脑免受大鼠局灶性脑缺血的影响
影响因子：
2.5
作者：
Kong, Ling-Lei;Hu, Jin-Feng;Chen, Nai-Hong
通讯作者：
Chen, Nai-Hong
影响因子：
15.1
作者：
Benakis, Corinne;Bonny, Christophe;Hirt, Lorenz
通讯作者：
Hirt, Lorenz