The essential involvement of cross-talk between IFN-γ and TGF-β in the skin wound-healing process
The essential involvement of cross-talk between IFN-γ and TGF-β in the skin wound-healing process
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DOI：
10.4049/jimmunol.172.3.1848
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发表时间：
2004-02-01
影响因子：
4.4
通讯作者：
Mukaida, N
中科院分区：
文献类型：
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作者：
Ishida, Y;Kondo, T;Mukaida, N
几条体外证据表明ifn - γ在血管生成和胶原沉积中的潜在作用，这是伤口愈合过程中的两个关键步骤。在本报告中，我们利用WT和ifn - γ KO小鼠研究了ifn - γ在皮肤伤口愈合过程中的作用。在WT小鼠中，切除性损伤通过浸润巨噬细胞和T细胞诱导ifn - γ mRNA和蛋白表达，同时IL-12和IL-18基因表达增强。与WT小鼠相比，ifn - γ KO小鼠的伤口愈合速度加快，伤口愈合速度加快，肉芽组织形成加快。此外，与WT小鼠相比，ifn - γ KO小鼠表现出血管新生增强，伤口部位血管内皮生长因子mRNA表达增强，尽管浸润性中性粒细胞、巨噬细胞和T细胞减少。与WT小鼠相比，ifn - γ KO小鼠也表现出胶原沉积加速，伤口部位tgf - β 1蛋白的产生增加。此外，ifn - γ的缺失增强了tgf - β(1)介导的信号通路，如总磷酸化Smad2水平的增加和Smad7水平的相应降低所证明的那样。这些结果表明，在伤口愈合过程中，ifn - γ /Stat1和tgf - β 1/Smad信号通路之间存在串扰。
Several lines of in vitro evidence suggest the potential role of IFN-gamma in angiogenesis and collagen deposition, two crucial steps in the wound healing process. In this report, we examined the role of IFN-gamma in the skin wound healing process utilizing WT and IFN-gamma KO mice. In WT mice, excisional wounding induced IFN-gamma mRNA and protein expression by infiltrating macrophages and T cells, with a concomitant enhancement of IL-12 and IL-18 gene expression. Compared with WT mice, IFN-gamma KO mice exhibited an accelerated wound healing as evidenced by rapid wound closure and granulation tissue formation. Moreover, IFN-gamma KO mice exhibited enhanced angiogenesis with augmented vascular endothelial growth factor mRNA expression in wound sites, compared with WT mice, despite a reduction in the infiltrating neutrophils, macrophages, and T cells. IFN-gamma KO mice also exhibited accelerated collagen deposition with enhanced production of TGF-beta1 protein in wound sites, compared with WT mice. Furthermore, the absence of IFN-gamma augmented the TGF-beta(1) -mediated signaling pathway, as evidenced by increases in the levels of total and phosphorylated Smad2 and a reciprocal decrease in the levels of Smad7. These results demonstrate that there is crosstalk between the IFN-gamma/Stat1 and TGF-beta1/Smad signaling pathways in the wound healing process.