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J.E. Sears, Q. Ebrahem, A. Minamoto, G. Hoppe, B. Anand–Apte; IL–6 Induced Angiogenesis is VEGF Dependent and Blocked by Triamcinolone Acetonide . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1760.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the molecular pathway for triamcinolone acetonide (TA) inhibition of IL–6 and VEGF mediated angiogenesis.
A rat cornea micropocket assay was utilized for IL–6 and VEGF mediated angiogenesis. Angiogenesis was quantified by measuring vessel length, vessel extension as well as vessel area. The phosphorylation of STAT3, the VEGF–R2, and ERK1/2 was determined by western blot in HUVEC lysates after 12 hours pretreatment with 1ug/ml TA followed by 10 minutes, 30 minutes and 6 hour stimulation with 50 ng/ml VEGF or 6 hour stimulation with 100ng/ml IL–6.
IL–6 induced corneal angiogenesis in a dose dependent manner, with 350 ngs producing peak angiogenesis at day 6. VEGF antibodies as well as coinsertion of a TA pellet blocked IL–6 mediated limbal neovascularization. TA also directly inhibited VEGF induced corneal angiogenesis when pellets of VEGF and TA were coinserted into cornea micropockets. TA did not inhibit IL–6 induced STAT3 phosphorylation at 6 hours and did not inhibit VEGF induced phosphorylation of the VEGF–R2 or ERK1/2 at 10 minutes, 30 minutes, and 6 hours in HUVECs.
IL–6 induced corneal neovascularization is VEGF dependent and blocked by TA. Although TA reduces the synthesis of VEGF during hypoxic and inflammatory stimulus, it also directly inhibits angiogenesis when VEGF is already present such as in these experiments using the cornea micropocket. The site of inhibition may be downstream of VEGF–R2.
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