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Won Soo Kim, Soo Jin Lee, Kyoung Woo Kim, Jae Chan Kim; Anti-inflammatory Effect of Angiogenin in Endotoxin-induced Uveitis Rat Model.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3500.
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© ARVO (1962-2015); The Authors (2016-present)
Previously, we revealed anti-inflammatory activity of angiogenin (ANG) in human corneal fibroblast cells inflammed by tumor necrosis factor (TNF)-α through an inhibition of TANK-binding kinase 1 (TBK1) mediated nuclear factor-κB (NF-κB) nuclear translocation. As a further study, we investigated the in vivo anti-inflammatory effect of ANG using the endotoxin-induced uveitis (EIU) rats.
EIU in Lewis rats was induced by lipopolysaccharide (LPS) injection in the footpad. EIU rats were treated by balanced salt solution (BSS group, 5 rats), 1% prednisolone acetate (PD group, 5 rats) or ANG (200 μg/ml; ANG group, 5 rats) 4 times a day. After 3 days, we enucleated both eyes, collected aqueous humor (AqH), and then analyzed number of infiltrating cells, protein concentration, inflammatory marker levels using immunodot blot assay. With enucleated eyes, we analyzed inflammatory cytokines, toll-like receptor (TLR)-4, myeloid differentiation factor (Myd) 88 expression using quantitative RT-PCR and Western blot analysis.
The levels of infiltrating leukocytes, protein concentration, and inflammatory cytokines and chemokines in the AqH were significantly elevated in the AqH of BSS group compared to the control. Then, PD and ANG significantly lowered all those inflammatory levels in the AqH. There was no difference between PD and ANG group. Additionally, TLR-4, Myd 88, IL-1β, 2, 4, 6 and, -10 in eyeball tissues were down-regulated by ANG.
These results suggest that ANG suppresses LPS-induced inflammatory responses in EIU rats through an inhibition of TLR-4 and Myd 88-related signals. ANG may be a novel therapeutic candidate in the ocular inflammatory condition.
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