Pro-inflammatory chemokine CCL2 (MCP-1) promotes healing in diabetic wounds by restoring the macrophage response.

Pro-inflammatory chemokine CCL2 (MCP-1) promotes healing in diabetic wounds by restoring the macrophage response.
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促炎趋化因子 CCL2 (MCP-1) 通过恢复巨噬细胞反应来促进糖尿病伤口的愈合。

DOI:
10.1371/journal.pone.0091574
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Shafikhani SH
Shafikhani SH
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wood S;Jayaraman V;Huelsmann EJ;Bonish B;Burgad D;Sivaramakrishnan G;Qin S;DiPietro LA;Zloza A;Zhang C;Shafikhani SH

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先前的研究表明,在糖尿病伤口中观察到的受损愈合源自持续性过度炎症状态,其特征在于包括巨噬细胞在内的炎性白细胞的有害增加。然而,这样的研究集中在伤口在较晚的时间点(第10天或以上),很少注意到巨噬细胞反应的动力学在糖尿病伤口损伤后早期。鉴于巨噬细胞对愈合过程的重要性,我们研究了糖尿病伤口愈合早期和晚期巨噬细胞反应的动力学。在这里,我们报告说,早期损伤后,糖尿病伤口表现出显着延迟巨噬细胞浸润。糖尿病伤口中巨噬细胞反应的延迟是由于趋化因子(C-C基序)配体2(CCL 2)表达减少所致。重要的是,用化学引诱物CCL 2的一次性治疗通过恢复巨噬细胞反应显著刺激糖尿病伤口的愈合。我们的数据表明,而不是一个高度炎症状态,早期糖尿病伤口表现出矛盾的和破坏性的减少基本的巨噬细胞反应。我们的研究表明,巨噬细胞反应的适当动力学的恢复可能能够启动随后的愈合阶段。基于CCL 2趋化因子的治疗可能是促进糖尿病伤口愈合的有吸引力的策略。
Prior studies suggest that the impaired healing seen in diabetic wounds derives from a state of persistent hyper-inflammation characterized by harmful increases in inflammatory leukocytes including macrophages. However, such studies have focused on wounds at later time points (day 10 or older), and very little attention has been given to the dynamics of macrophage responses in diabetic wounds early after injury. Given the importance of macrophages for the process of healing, we studied the dynamics of macrophage response during early and late phases of healing in diabetic wounds. Here, we report that early after injury, the diabetic wound exhibits a significant delay in macrophage infiltration. The delay in the macrophage response in diabetic wounds results from reduced Chemokine (C-C motif) ligand 2 (CCL2) expression. Importantly, one-time treatment with chemoattractant CCL2 significantly stimulated healing in diabetic wounds by restoring the macrophage response. Our data demonstrate that, rather than a hyper-inflammatory state; the early diabetic wound exhibits a paradoxical and damaging decrease in essential macrophage response. Our studies suggest that the restoration of the proper kinetics of macrophage response may be able to jumpstart subsequent healing stages. CCL2 chemokine-based therapy may be an attractive strategy to promote healing in diabetic wounds.
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