Dysregulation of monocyte/macrophage phenotype in wounds of diabetic mice
Dysregulation of monocyte/macrophage phenotype in wounds of diabetic mice
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DOI：
10.1016/j.cyto.2011.06.016
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发表时间：
2011-11-01
期刊：
影响因子：
3.8
通讯作者：
Koh, Timothy J.
中科院分区：
文献类型：
--
作者：
Mirza, Rita;Koh, Timothy J.
本研究的假设是单核细胞/巨噬细胞谱系（Mo/Mp）的细胞在糖尿病小鼠的伤口中表现出从促炎表型到促愈合表型的受损转变，这有助于愈合不足。从非糖尿病db/+小鼠的切除伤口中分离的Mo/Mp在损伤后第5天表现出促炎表型，促炎分子白细胞介素-1 β、基质金属蛋白酶-9和诱导型一氧化氮合酶的高水平表达。创伤Mo/Mp在损伤后第10天表现出较少的炎性表型，促炎分子的表达降低，替代活化标志物CD 206和CD 36的表达增加。相反，在db/db小鼠中，促炎表型持续到损伤后第10天，并且与胰岛素样生长因子-1、转化生长因子-β 1和血管内皮生长因子的表达减少相关。db/db小鼠伤口中这些生长因子水平的降低可能导致伤口闭合受损、肉芽组织形成减少、血管生成和胶原沉积。db/db小鼠中持续的促炎性伤口Mo/Mp表型可能是由于伤口环境中促炎性白细胞介素-1 β和干扰素-γ水平升高以及抗炎性白细胞介素-10水平降低所致。我们的研究结果与Mo/Mp表型失调导致糖尿病伤口愈合受损的假设一致。(C)2011爱思唯尔有限公司保留所有权利。
The hypothesis of this study was that cells of the monocyte/macrophage lineage (Mo/Mp) exhibit an impaired transition from pro-inflammatory to pro-healing phenotypes in wounds of diabetic mice, which contributes to deficient healing. Mo/Mp isolated from excisional wounds in non-diabetic db/+ mice exhibited a pro-inflammatory phenotype on day 5 post-injury, with high level expression of the pro-inflammatory molecules interleukin-1 beta, matrix metalloprotease-9 and inducible nitric oxide synthase. Wound Mo/Mp exhibited a less inflammatory phenotype on day 10 post-injury, with decreased expression of the pro-inflammatory molecules and increased expression of the alternative activation markers CD206 and CD36. In contrast, in db/db mice, the pro-inflammatory phenotype persisted through day 10 post-injury and was associated with reduced expression of insulin-like growth factor-1, transforming growth factor-beta 1 and vascular endothelial growth factor. Reduced levels of these growth factors in wounds of db/db mice may have contributed to impaired wound closure, reduced granulation tissue formation, angiogenesis and collagen deposition. The persistent pro-inflammatory wound Mo/Mp phenotype in db/db mice may have resulted from elevated levels of pro-inflammatory interleukin-1 beta and interferon-gamma and reduced levels of anti-inflammatory interleukin-10 in the wound environment. Our findings are consistent with the hypothesis that dysregulation of Mo/Mp phenotypes contributes to impaired healing of diabetic wounds. (C) 2011 Elsevier Ltd. All rights reserved.