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Erythropoietin-derived nonerythropoietic peptide ameliorates experimental autoimmune neuritis by inflammation suppression and tissue protection.
- Source :
-
PloS one [PLoS One] 2014 Mar 06; Vol. 9 (3), pp. e90942. Date of Electronic Publication: 2014 Mar 06 (Print Publication: 2014). - Publication Year :
- 2014
-
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.
- Subjects :
- Animals
Cell Differentiation drug effects
Cell Proliferation drug effects
Inflammation chemically induced
Inflammation drug therapy
Inflammation immunology
Inflammation pathology
Injections, Intraperitoneal
Injections, Subcutaneous
Male
Neuritis, Autoimmune, Experimental chemically induced
Neuritis, Autoimmune, Experimental immunology
Neuritis, Autoimmune, Experimental pathology
Neuropeptides adverse effects
Neuroprotective Agents chemical synthesis
Oligopeptides chemical synthesis
Rats
Rats, Inbred Lew
Sciatic Nerve drug effects
Sciatic Nerve immunology
Sciatic Nerve pathology
T-Lymphocytes, Helper-Inducer drug effects
T-Lymphocytes, Helper-Inducer immunology
T-Lymphocytes, Helper-Inducer pathology
T-Lymphocytes, Regulatory drug effects
T-Lymphocytes, Regulatory immunology
T-Lymphocytes, Regulatory pathology
Th1-Th2 Balance drug effects
Erythropoietin chemistry
Nerve Regeneration drug effects
Neuritis, Autoimmune, Experimental drug therapy
Neuroprotective Agents pharmacology
Oligopeptides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 9
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 24603865
- Full Text :
- https://doi.org/10.1371/journal.pone.0090942