title: Erythropoietin-derived nonerythropoietic peptide ameliorates experimental autoimmune neuritis by inflammation suppression and tissue protection.
abstract: Experimental autoimmune neuritis (EAN) is an autoantigen-specific T-cell-mediated disease model for human demyelinating inflammatory disease of the peripheral nervous system. Erythropoietin (EPO) has been known to promote EAN recovery but its haematopoiesis stimulating effects may limit its clinic application. Here we investigated the effects and potential mechanisms of an EPO-derived nonerythropoietic peptide, ARA 290, in EAN. Exogenous ARA 290 intervention greatly improved EAN recovery, improved nerve regeneration and remyelination, and suppressed nerve inflammation. Furthermore, haematopoiesis was not induced by ARA 290 during EAN treatment. ARA 290 intervention suppressed lymphocyte proliferation and altered helper T cell differentiation by inducing increase of Foxp3+/CD4+ regulatory T cells and IL-4+/CD4+ Th2 cells and decrease of IFN-γ+/CD4+ Th1 cells in EAN. In addition, ARA 290 inhibited inflammatory macrophage activation and promoted its phagocytic activity. In vitro, ARA 290 was shown to promote Schwann cell proliferation and inhibit its inflammatory activation. In summary, our data demonstrated that ARA 290 could effectively suppress EAN by attenuating inflammation and exerting direct cell protection, indicating that ARA 290 could be a potent candidate for treatment of autoimmune neuropathies.
authors.affiliation: Institute of Immunology, Third Military Medical University of People's Liberation Army, Chongqing, China.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Immunology, Third Military Medical University of People's Liberation Army, Chongqing, China.
authors.forename: Bangwei
authors.initials: B
authors.lastname: Luo
authors.affiliation: Institute of Immunology, Third Military Medical University of People's Liberation Army, Chongqing, China.
authors.forename: Fuyu
authors.initials: F
authors.lastname: Han
authors.affiliation: Institute of Immunology, Third Military Medical University of People's Liberation Army, Chongqing, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Immunology, Third Military Medical University of People's Liberation Army, Chongqing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Institute of Immunology, Third Military Medical University of People's Liberation Army, Chongqing, China.
authors.forename: Man
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Institute of Immunology, Third Military Medical University of People's Liberation Army, Chongqing, China.
authors.forename: Xioafeng
authors.initials: X
authors.lastname: Yang
authors.affiliation: Institute of Immunology, Third Military Medical University of People's Liberation Army, Chongqing, China.
authors.forename: Yuzhang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Institute of Immunology, Third Military Medical University of People's Liberation Army, Chongqing, China.
authors.forename: Zhiren
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004921:Erythropoietin / Q000737:chemistry*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects*; D009444:Neuritis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D009479:Neuropeptides / Q000009:adverse effects; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D058408:Th1-Th2 Balance / Q000187:drug effects
chemical_list: D009479:Neuropeptides; D018696:Neuroprotective Agents; D009842:Oligopeptides; D004921:Erythropoietin; C576178:cibinetide