ROLE OF RETINAL PIGMENT EPITHELIUM IN RETINAL DISORDERS

视网膜色素上皮在视网膜疾病中的作用

• 批准号: 6106845
• 负责人: Chandrasek N Nagineni
• 金额: --
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6106845
• 关键词: Toxoplasma gondii; cell adhesion molecules; chorioretinitis; cytokine; enzyme induction /repression; eye infections; gel mobility shift assay; human tissue; inflammation; interferon gamma; interleukin 1; interleukin 6; nitric oxide; northern blottings; ocular toxoplasmosis; polymerase chain reaction; retina disorder; retinal pigment epithelium; tissue /cell culture; transcription factor; transforming growth factors; tumor necrosis factor alpha; uveitis

Human retinal pigment epithelial (HRPE) cell cultures were used as a model to investigate the various roles of HRPE in the pathophysiology of retinal disorders. We have recently reported that HRPE cells upregulate mRNA levels and secrete significant quantities of interleukin (IL) -6, intercellular adhesion molecule-1 (ICAM-1), granulocyte macrophage colony stimulating factor (GMCSF) and nitric oxide in response to the stimulation by inflammatory mediators interferon (IFN) gamma, IL-1 and tumor necrosis factor (TNF) -alpha. Signaling pathways of IFN-gamma in HRPE cells were evaluated to delineate the mechanisms of IFN-gamma action. Transcription factors IRF-1 and IRF-2 (interferon regulatory factors), but not ICSBP (interferon consensus sequence binding protein), were induced by IFN-gamma in HRPE cells. Electrophoretic mobility shift and supershift assays revealed that activation of IRF genes is mediated by STAT-1, a member of signal transducers and activators of transcription. Inflammation associated with retinochoroiditis due to ocular toxoplasmosis (OT) is one of the common causes of uveitis. In immunocompromised individuals such as AIDS patients and transplant recipients, OT may result in loss of vision. We have previously shown that Toxoplasma gondii (TG) can replicate in HRPE cells and the inhibition of replication by interferons. We have conducted studies to investigate the responses of HRPE cells in cytokine production during TG invasion and intracellular replication. TG infection of HRPE cells resulted in 5 to 20 fold increase in the secretion of IL-1, IL-6, GMCSF as well as ICAM-1. Northern blot and RT-PCR analyses indicated enhanced mRNA levels suggesting activation at transcriptional stage. However, secretion of IL-4, IL-10, IL-12, IL-15 or nitric oxide was not observed. The secretion of these cytokines by HRPE cells during TG infection suggests that cytokines play a critical role in the pathogenesis of TG induced retinochoroiditis.

人视网膜色素上皮(HRPE)细胞培养 研究hRPE在病理生理学中不同作用的模型 视网膜疾病的症状。我们最近报道了hRPE细胞 上调mRNA水平并分泌大量的 白介素6、细胞间黏附分子-1、 粒细胞巨噬细胞集落刺激因子与一氧化氮 氧化物对炎症介质刺激的反应 干扰素、IL-1、肿瘤坏死因子-α。 HRPE细胞中干扰素-γ的信号通路被评估为 阐明了干扰素-γ的作用机制。转录因子 IRF-1和IRF-2(干扰素调节因子)，但不是ICSBP (干扰素共有序列结合蛋白)，由 HRPE细胞中的干扰素-γ。电泳迁移率漂移和 超位移分析表明，IRF基因的激活是由 通过STAT-1，信号换能器和激活器的成员 抄写。 眼部视网膜脉络膜炎相关炎症 弓形虫病(OT)是葡萄膜炎的常见病因之一。在……里面 免疫功能受损的个人，如艾滋病患者和移植患者 受者，OT可能会导致失明。我们之前已经 弓形虫(Tg)可在人视网膜色素上皮细胞中复制 干扰素对复制的抑制。我们已经进行了 人视网膜色素上皮细胞对细胞因子反应的研究 在TG侵入和细胞内复制过程中产生。TG 感染人视网膜色素上皮细胞可使人视网膜色素上皮细胞 分泌IL-1、IL-6、GMCSF和ICAM-1。Northern印迹和 RT-PCR分析显示mRNA水平升高，提示激活 在转录阶段。而IL-4、IL-10、IL-12、 未观察到IL-15和一氧化氮。这些物质的分泌物 甘油三酯感染期间hRPE细胞的细胞因子提示细胞因子 甘油三酯在甘油三酯致病机制中的作用 视网膜脉络膜炎。