IFN-gamma acts as anti-angiogenic cytokine in the human cornea by regulating the expression of VEGF-A and sVEGF-R1.

IFN-gamma acts as anti-angiogenic cytokine in the human cornea by regulating the expression of VEGF-A and sVEGF-R1.
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DOI:
10.1016/j.bbrc.2008.07.042
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发表时间:
2008-09-26
影响因子:
3.1
通讯作者:
Hooks, John J.
Hooks, John J.
中科院分区:
生物学4区
文献类型:
--
作者:
Kommineni, Vijay K.;Nagineni, Chandrasekharam N.;William, Abitha;Detrick, Barbara;Hooks, John J.

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已知角膜内的炎症过程与角膜新生血管(CN)有关。我们研究了炎症介质对角膜细胞血管生成因子表达的影响。TNF-α和IL-1诱导角膜成纤维细胞(HCRF)分泌VEGF-A, IFN-γ显著抑制这种分泌。由角膜上皮细胞(HCE)组成的VEGF-A不受这些细胞因子的影响。此外,IFN-γ显著刺激HCRF分泌sVEGF-R1(sFlt-1)。JAK-STAT通路抑制剂逆转了IFN-γ对HCRF中VEGF-A和sFlt-1分泌的影响。RT-PCR分析显示,IFN-γ通过影响VEGF-A和sFlt-1 mRNA水平影响VEGF-A和sFlt-1的表达。IFN-γ抑制TGF-β诱导的VEGF-A分泌,但不抑制svegf - r1分泌。这是首次报道IFN-γ分别抑制和刺激VEGF-A和sFlt-1的分泌。我们的研究结果表明,IFN-γ在人角膜中作为一种抗血管生成的细胞因子。
Inflammatory processes within the cornea are known to be associated with corneal neovascularization (CN). We examined the effects of inflammatory mediators on the expression of angiogenic factors by corneal cells. TNF-α and IL-1 induced VEGF-A secretion by corneal fibroblasts (HCRF) and this was inhibited significantly by IFN-γ. Constitutively secreted VEGF-A by corneal epithelial cells (HCE) was not affected by these cytokines. Moreover, sVEGF-R1(sFlt-1) secretion by HCRF was stimulated significantly by IFN-γ. JAK-STAT pathway inhibitor reversed the effects of IFN-γ on VEGF-A and sFlt-1 secretion by HCRF. RT-PCR analysis showed that IFN-γ influences the expression of VEGF-A and sFlt-1 by affecting their mRNA level. IFN-γ inhibited TGF-β induced VEGF-A secretion but not sVEGF-R1secretion. This is the first report demonstrating the inhibitory and stimulatory effects of IFN-γ on VEGF-A and sFlt-1 secretion, respectively. Our results suggest that IFN-γ acts as an anti-angiogenic cytokine in the human cornea.
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