IFN-gamma acts as anti-angiogenic cytokine in the human cornea by regulating the expression of VEGF-A and sVEGF-R1.
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 cytokine in the human cornea.
Kommineni
Vijay K
VK
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Building 7, Room 200, 7 Memorial Drive, Bethesda, MD 20892, USA.
Nagineni
Chandrasekharam N
CN
William
Abitha
A
Detrick
Barbara
B
Hooks
John J
JJ
D002460:Cell Line; D003315:Cornea / Q000187:drug effects / Q000201:enzymology*; D016510:Corneal Neovascularization / Q000201:enzymology*; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology / Q000502:physiology*; D007375:Interleukin-1 / Q000494:pharmacology; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000096:biosynthesis; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000819:agonists* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism
D007375:Interleukin-1; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D007371:Interferon-gamma; D051496:Receptor, Fibroblast Growth Factor, Type 1; D053613:Janus Kinase 1