Erythropoietin is a hypoxia inducible factor-induced protective molecule in experimental autoimmune neuritis

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1832

Article

Luo, Bangwei¹  Jiang, Man¹  Yang, Xiaofeng¹  Zhang, Zhiyuan²  Xiong, Jian¹  Schluesener, Hermann J.²  Zhang, Zhiren¹  Wu, Yuzhang¹ 

[1] Third Mil Med Univ PLA, Inst Immunol, Chongqing 400038, Peoples R China

[2] Univ Tubingen, Div Immunopathol Nervous Syst, D-72076 Tubingen, Germany

关键词: Erythropoietin;    Experimental autoimmune neuritis;    Inflammation;    Schwann cell;    T cell;    Macrophage;   

DOI  :  10.1016/j.bbadis.2013.04.015

来源: Elsevier

【 摘 要 】

Experimental autoimmune neuritis (EAN), an autoantigen-specific T-cell-mediated disease model for human demyelinating inflammatory disease of the peripheral nervous system, is characterized by self-limitation. Here we investigated the regulation and contribution of erythropoietin (EPO) in EAN self-limitation. In EAN sciatic nerves, hypoxia, and protein and mRNA levels of hypoxia-inducible factor 1 alpha (HIF-1 alpha), HIF-2 alpha, EPO and EPO receptor (EPOR) were induced in parallel at disease peak phase but reduced at recovery periods. Further, the deactivation of HIF reduced EAN-induced EPO/EPOR upregulation in EAN, suggesting the central contribution of HIF to EPO/EPOR induction. The deactivation of EPOR signalling exacerbated EAN progression, implying that endogenous EPO contributed to EAN recovery. Exogenous EPO treatment greatly improved EAN recovery. In addition, EPO was shown to promote Schwann cell survival and myelin production. In EAN, EPO treatment inhibited lymphocyte proliferation and altered helper T cell differentiation by inducing increase of Foxp3(+)/CD4(+) regulatory T cells and decrease of IFN-gamma(+)/CD4(+) Th1 cells. Furthermore, EPO inhibited inflammatory macrophage activation and promoted its phagocytic activity. In summary, our data demonstrated that EPO was induced in EAN by HIF and contributed to EAN recovery, and endogenous and exogenous EPO could effectively suppress EAN by attenuating inflammation and exerting direct cell protection, indicating that EPO contributes to the self-recovery of EAN and could be a potent candidate for treatment of autoimmune neuropathies. (C) 2013 Elsevier B.V. All rights reserved.

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