期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 374, 期 3, 页码 479-484出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2008.07.042
关键词
IFN-gamma; VEGF-A; sVEGF-R1; cornea; fibroblasts; corneal neovascularization; inflammation; IL-1; TNF-alpha
资金
- National Eye Institute, National Institutes of Health
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-alpha and IL-1 induced VEGF-A secretion by corneal fibroblasts (HCRF) and this was inhibited significantly by IFN-gamma. 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-gamma. JAK-STAT pathway inhibitor reversed the effects of IFN-gamma on VEGF-A and sFlt-1 secretion by HCRF. RT-PCR analysis showed that IFN-gamma influences the expression of VEGF-A and sFlt-1 by affecting their mRNA level. IFN-gamma inhibited TGF-beta induced VEGF-A secretion but not sVEGF-R1 secretion. This is the first report demonstrating the inhibitory and stimulatory effects of IFN-gamma on VEGF-A and sFlt-1 secretion, respectively. Our results suggest that IFN-gamma acts as an anti-angiogenic cyrokine in the human cornea. Published by Elsevier Inc.
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