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

Vijay K. Kommineni, Chandrasekharam N. Nagineni, Abitha William, Barbara Detrick, John J. Hooks

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)479-484
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume374
Issue number3
DOIs
StatePublished - Sep 26 2008

Keywords

  • Cornea
  • Corneal neovascularization
  • Fibroblasts
  • IFN-γ
  • IL-1
  • Inflammation
  • TNF-α
  • VEGF-A
  • sVEGF-R1

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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