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: Yuqi Liu, Bangwei Luo, Fuyu Han, Xiaoming Li, Jian Xiong, Man Jiang, Xioafeng Yang, Yuzhang Wu, Zhiren Zhang
• Journal: PloS one (PLoS One) Vol. 9 Issue 3 Pg. e90942 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24603865 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neuropeptides
• Neuroprotective Agents
• Oligopeptides
• Erythropoietin
• cibinetide

Topics

• Animals
• Cell Differentiation (drug effects)
• Cell Proliferation (drug effects)
• Erythropoietin (chemistry)
• Inflammation (chemically induced, drug therapy, immunology, pathology)
• Injections, Intraperitoneal
• Injections, Subcutaneous
• Male
• Nerve Regeneration (drug effects)
• Neuritis, Autoimmune, Experimental (chemically induced, drug therapy, immunology, pathology)
• Neuropeptides (adverse effects)
• Neuroprotective Agents (chemical synthesis, pharmacology)
• Oligopeptides (chemical synthesis, pharmacology)
• Rats
• Rats, Inbred Lew
• Sciatic Nerve (drug effects, immunology, pathology)
• T-Lymphocytes, Helper-Inducer (drug effects, immunology, pathology)
• T-Lymphocytes, Regulatory (drug effects, immunology, pathology)
• Th1-Th2 Balance (drug effects)