Hata Y, Sassa Y, Kita T, Miura M, Kano K, Kawahara S, Arita R, Nakao S, Shih J L, Ishibashi T
Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Br J Ophthalmol. 2008 Nov;92(11):1540-4. doi: 10.1136/bjo.2008.141002.
Tumour necrosis factor-alpha (TNF-alpha) is one of the major inflammatory cytokines involved in the pathogenesis of various vitreoretinal diseases. The authors investigated the effect of hypoxia, TNF-alpha and dexamethasone on vascular endothelial growth factor (VEGF) expression by cultured hyalocytes.
Hyalocytes were isolated from bovine vitreous. Hypoxic and TNF-alpha-dependent effects on cultured hyalocytes were investigated using several assays to determine VEGF protein expression, hypoxia-inducible factor (HIF)-1alpha protein levels, HIF-1alpha-DNA-binding ability and VEGF mRNA stability. The effects of dexamethasone on VEGF expression and its intracellular signalling under hypoxic or TNF-alpha stimulated conditions were also examined.
Hypoxic conditions and TNF-alpha stimulation induce VEGF expression in hyalocytes. These stimuli also stabilise HIF-1alpha protein and increase its DNA-binding ability. Dexamethasone significantly inhibits both HIF-1alpha protein levels and HIF-1alpha-DNA-binding activity, and also decreases the hypoxic- and TNF-alpha -dependent induction of VEGF expression in hyalocyte. However, dexamethasone has no significant effect on the stability of VEGF mRNA.
Hyalocytes may be involved in various vitreoretinal diseases by increasing HIF-1alpha protein stability and HIF-1alpha-DNA binding, and thus increasing VEGF production under pathological conditions. Dexamethasone seems to be capable of inhibiting hypoxic and TNF-alpha dependent VEGF production, presumably via its inhibitory effects on HIF-1alpha protein levels and its DNA-binding activity.
肿瘤坏死因子-α（TNF-α）是参与多种玻璃体视网膜疾病发病机制的主要炎症细胞因子之一。作者研究了缺氧、TNF-α和地塞米松对培养的玻璃体细胞血管内皮生长因子（VEGF）表达的影响。
从牛玻璃体中分离出玻璃体细胞。使用多种测定方法研究缺氧和TNF-α对培养的玻璃体细胞的影响，以确定VEGF蛋白表达、缺氧诱导因子（HIF）-1α蛋白水平、HIF-1α与DNA的结合能力以及VEGF mRNA稳定性。还检测了地塞米松在缺氧或TNF-α刺激条件下对VEGF表达及其细胞内信号传导的影响。
缺氧条件和TNF-α刺激可诱导玻璃体细胞中VEGF的表达。这些刺激还可稳定HIF-1α蛋白并增加其与DNA的结合能力。地塞米松可显著抑制HIF-1α蛋白水平和HIF-1α与DNA的结合活性，还可降低缺氧和TNF-α依赖性诱导的玻璃体细胞中VEGF的表达。然而，地塞米松对VEGF mRNA的稳定性没有显著影响。
玻璃体细胞可能通过增加HIF-1α蛋白稳定性和HIF-1α与DNA的结合，从而在病理条件下增加VEGF的产生，参与多种玻璃体视网膜疾病。地塞米松似乎能够抑制缺氧和TNF-α依赖性VEGF的产生，可能是通过其对HIF-1α蛋白水平及其与DNA结合活性的抑制作用。
