Kutty R Krishnan, Samuel William, Abay Rebecca, Cherukuri Aswini, Nagineni Chandrasekharam N, Duncan Todd, Jaworski Cynthia, Vijayasarathy Camasamudram, Redmond T Michael
Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, United States.
Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, United States.
Cytokine. 2015 Aug;74(2):335-8. doi: 10.1016/j.cyto.2015.03.016. Epub 2015 Apr 15.
Dysfunction of the retinal pigment epithelium (RPE) resulting from chronic inflammation is implicated in the pathogenesis of age-related macular degeneration (AMD). RPE cells adjacent to drusen deposits in the AMD eye are known to contain CXCL11, a chemokine involved in inflammatory cell recruitment. We investigated the CXCL11 production by the human RPE (ARPE-19) cells under inflammatory conditions and tested its response to resveratrol, a naturally occurring anti-inflammatory antioxidant. A proinflammatory cytokine mixture consisting of IFN-γ, IL-1β and TNF-α highly increased CXCL11 mRNA expression and CXCL11 protein secretion by ARPE-19 cells. Resveratrol substantially inhibited the proinflammatory cytokines-induced CXCL11 production while partially blocking nuclear factor-κB activation. This inhibitory action of resveratrol was also observed for the cytokines-induced expression of chemokines CXCL9, CCL2 and CCL5. Our results indicate that resveratrol could potentially attenuate RPE inflammatory response implicated in the pathogenesis of AMD.
慢性炎症导致的视网膜色素上皮(RPE)功能障碍与年龄相关性黄斑变性(AMD)的发病机制有关。已知AMD眼中与玻璃膜疣沉积物相邻的RPE细胞含有CXCL11,这是一种参与炎症细胞募集的趋化因子。我们研究了炎症条件下人RPE(ARPE-19)细胞中CXCL11的产生,并测试了其对白藜芦醇(一种天然存在的抗炎抗氧化剂)的反应。由IFN-γ、IL-1β和TNF-α组成的促炎细胞因子混合物显著增加了ARPE-19细胞中CXCL11 mRNA的表达和CXCL11蛋白的分泌。白藜芦醇显著抑制促炎细胞因子诱导的CXCL11产生,同时部分阻断核因子-κB的激活。在细胞因子诱导的趋化因子CXCL9、CCL2和CCL5的表达中也观察到了白藜芦醇的这种抑制作用。我们的结果表明,白藜芦醇可能会减弱与AMD发病机制相关的RPE炎症反应。