Erythropoietin Contrastingly Affects Bacterial Infection and Experimental Colitis by Inhibiting Nuclear Factor-κB-Inducible Immune Pathways

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• 作者：Manfred Nairz¹ ; Andrea Schroll¹ ; Alexander R. Moschen² ; Thomas Sonnweber¹ ; Milan Theurl¹ ; ³ ; Igor Theurl¹ ; Nicole Taub⁴ ; Christina Jamnig¹ ; Daniela Neurauter¹ ; Lukas A. Huber⁴ ; Herbert Tilg² ; Patrizia L. Moser⁵ ; Gü ; nter Weiss¹ ; ^{guenter.weiss@i-med.ac.at}
• 刊名：Immunity
• 出版年：2011
• 出版时间：28 January 2011
• 年：2011
• 卷：34
• 期：1
• 页码：61-74
• 全文大小：2663 K

文摘

Summary

Erythropoietin (EPO) is the principal cytokine regulating erythropoiesis through its receptor, EPOR. Interestingly, EPORs are also found on immune cells with incompletely understood functions. Here, we show that EPO inhibits the induction of proinflammatory genes including tumor necrosis factor (TNF)-α and inducible nitric oxide (NO) synthase in activated macrophages, which is mechanistically attributable to blockage of nuclear factor (NF)-κB p65 activation by EPO. Accordingly, in systemic Salmonella infection, treatment of mice with EPO results in reduced survival and impaired pathogen clearance because of diminished formation of anti-microbial effector molecules such as TNF-α and NO. However, neutralization of endogenous EPO or genetic ablation of Epor promotes Salmonella elimination. In contrast, in chemically induced colitis, EPO-EPOR interaction decreases the production of NF-κB-inducible immune mediators, thus limiting tissue damage and ameliorating disease severity. These immune-modulatory effects of EPO may be of therapeutic relevance in infectious and inflammatory diseases.

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