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EPO attenuates inflammatory cytokines by Muller cells in diabetic retinopathy
Journal article   Open access   Peer reviewed

EPO attenuates inflammatory cytokines by Muller cells in diabetic retinopathy

Xia Lei, Jingfa Zhang, Jianfeng Shen, Liu-Mei Hu, Yalan Wu, Lisha Mou, Guoxu Xu, Weiye Li and Guo-Tong Xu
Frontiers in bioscience (Elite edition), v 3(1), pp 201-211
01 Jan 2011
PMID: 21196299
url
https://doi.org/10.2741/e234View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze) Open

Abstract

Animals Cell Line Cytokines - immunology Cytokines - metabolism Diabetes Mellitus, Experimental - complications Diabetic Retinopathy - etiology Diabetic Retinopathy - immunology Diabetic Retinopathy - metabolism Enzyme-Linked Immunosorbent Assay Erythropoietin - pharmacology Gene Expression Regulation - immunology In Situ Nick-End Labeling Interleukin-1beta - metabolism Interleukin-6 - metabolism Luciferases NF-kappa B - metabolism Rats Reverse Transcriptase Polymerase Chain Reaction Tetrazolium Salts Thiazoles Transcription Factor AP-1 - metabolism Tumor Necrosis Factor-alpha - metabolism Vascular Endothelial Growth Factor A - metabolism
Diabetic retinopathy (DR) is a chronic, low-grade inflammatory disease. We aimed to investigate the regulatory effects of erythropoietin (EPO) on the inflammatory cytokine production by Muller cells under the condition of DR. The expression levels of TNF-alpha, IL-1beta, IL-6 and VEGF in cultured rat Muller cells were enhanced by 1 mM glyoxal. The elevated TNF-alpha and IL-1beta, but not IL-6 and VEGF, were decreased by 2 U/ml EPO as detected by real-time PCR and ELISA. Moreover, the activity of AP-1 but not NF-kappaB was modulated by glyoxal and EPO. Intravitreal injection of EPO performed 24 h prior to sacrifice significantly reduced TNF-alpha and IL-1beta production while moderately attenuating IL-6 and VEGF in the retinas of streptozotocin-induced diabetic rats. Furthermore, Muller cells were identified as the main source of IL-1beta production as indicated by co-localization of IL-1beta and CRALBP in situ. These findings implicate therapeutic potential of EPO in the amelioration of inflammation in diabetic retinas.

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