Fibroblasts regulate monocyte response to ECM-derived matrix: the effects on monocyte adhesion and the production of inflammatory, matrix remodeling, and growth factor proteins.

Fibroblasts regulate monocyte response to ECM-derived matrix: the effects on monocyte adhesion and the production of inflammatory, matrix remodeling, and growth factor proteins.
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DOI:
10.1002/jbm.a.32431
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发表时间:
2009-06-15
影响因子:
4.9
通讯作者:
Kao, Weiyuan John
Kao, Weiyuan John
中科院分区:
工程技术3区
文献类型:
--
作者:
Chung, Amy S.;Kao, Weiyuan John

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单核细胞/巨噬细胞和成纤维细胞被募集到损伤部位并协调宿主反应和组织修复。我们之前已经证明,将聚乙二醇(PEG)化的精氨酸-甘氨酸-天冬氨酸(RGD)序列移植到基于细胞外基质(ECM)的半互穿网络(sIPN)上可以增强单核细胞粘附,并调节随后的基因表达以及炎症和基质重塑因子的释放。在这项研究中,我们研究了成纤维细胞对单核细胞对此 ECM 模拟物反应的直接影响。分析炎症、基质重塑和再生中的关键伤口愈合因素,以深入了解成纤维细胞-单核细胞相互作用中调节的相互关联作用。白细胞介素-1α/-1β (IL-1α/-1β)、白细胞介素-6 (IL-6)、肿瘤坏死因子-α (TNF-α)、单核细胞炎症蛋白-1α/-1β (MIP-1α/-1β)、转化生长因子-α (TGF-α)、单核细胞趋化因子 (MCP-1)、基质金属蛋白酶-2/-9分析了 (MMP-2/−9)、血管内皮生长因子 (VEGF)、粒细胞-巨噬细胞集落刺激因子 (GM-CSF)。随着时间的推移,成纤维细胞减少了单核细胞对 RGD 移植的 sIPN 的粘附,同时增加了所有表面上的单核细胞 GM-CSF,除了 96 小时时的 RGD 和 PHSRN 移植的 sIPN 上。单核细胞降低了初始成纤维细胞IL-1α和TGF-α,但显着增加了成纤维细胞MMP-2和GM-CSF。在所有 sIPN 存在的情况下,单核细胞 IL-1β、TNF-α、MIP-1β、MCP-1、MMP-9 和 GM-CSF 表达随着时间的推移而增加,并且当 sIPN 用配体固定时,与未修饰的 sIPN 相比,观察到成纤维细胞 IL-1β、MIP-1α、MIP-1β 的下调。当固定的配体为RGD时,在选定的时间点单核细胞TGF-α、MIP-1β和VEGF表达增加,而单核细胞GM-CSF表达减少。这些结果表明,在成纤维细胞存在的情况下,单核细胞对选定的 ECM 成分有动态反应。
Monocytes/macrophages and fibroblasts are recruited to the injury site and orchestrate the host response and tissue repair. We have previously shown that polyethylene glycol (PEG)-ylated arginine-glycine-aspartic acid (RGD) sequence grafted onto an extracellular matrix (ECM)-based semi-interpenetrating network (sIPN) enhances monocyte adhesion, and modulates subsequent gene expression and release of inflammatory and matrix remodeling factors. In this study, we investigate the direct influence of fibroblasts on monocyte response to this ECM mimic. Key wound-healing factors in inflammation, matrix remodeling, and regeneration were analyzed to gain insight into the interrelated role of regulation in fibroblast-monocyte interaction. Interleukin-1alpha/−1beta (IL-1α/−1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte inflammatory protein-1alpha/−1beta (MIP-1α/−1β), transforming growth factor-alpha (TGF-α), monocyte chemoattractant factor (MCP-1), matrix metalloproteinase-2/−9 (MMP-2/−9), vascular endothelial growth factor (VEGF), granulocyte-macrophage colony-stimulating factor (GM-CSF) were analyzed. Fibroblasts decreased monocyte adhesion onto the RGD-grafted sIPN while increasing monocyte GM-CSF on all surfaces over time except for on RGD and PHSRN-grafted sIPN at 96 h. Monocytes decreased initial fibroblast IL-1α and TGF-α, but drastically increased fibroblast MMP-2 and GM-CSF. Monocyte IL-1β, TNF-α, MIP-1β, MCP-1, MMP-9, and GM-CSF expression was increased over time in the presence of all sIPNs, and when the sIPNs were immobilized with ligands, a down-regulation of fibroblast IL-1β, MIP-1α, MIP-1β compared with unmodified sIPN was observed. When the ligand immobilized was RGD, monocyte TGF-α, MIP-1β, and VEGF expression was increased while monocyte GM-CSF was decreased at selected time points. These results showed a dynamic monocyte response to selected ECM components in the presence of fibroblasts.
DOI: 10.1189/jlb.0605318
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作者:
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