Erythropoietin-derived Nonerythropoietic Peptide Ameliorates Experimental Autoimmune Neuritis by Inflammation Suppression and Tissue Protection

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Mar 8

PMID 24603865

Citations 15

Authors

Yuqi Liu

Bangwei Luo

Fuyu Han

Xiaoming Li

Jian Xiong

Man Jiang

Xioafeng Yang

Yuzhang Wu

Zhiren Zhang

Affiliations

Soon will be listed here.

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.

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References

van Rijt W, Nieuwenhuijs-Moeke G, Goor H, Jespersen B, Ottens P, Ploeg R . ARA290, a non-erythropoietic EPO derivative, attenuates renal ischemia/reperfusion injury. J Transl Med. 2013; 11:9. PMC: 3567997. DOI: 10.1186/1479-5876-11-9. View

Zhang Z, Zhang Z, Schluesener H . FTY720 attenuates lesional interleukin-17(+) cell accumulation in rat experimental autoimmune neuritis. Neuropathol Appl Neurobiol. 2009; 35(5):487-95. DOI: 10.1111/j.1365-2990.2009.01016.x. View

Swartjes M, Morariu A, Niesters M, Brines M, Cerami A, Aarts L . ARA290, a peptide derived from the tertiary structure of erythropoietin, produces long-term relief of neuropathic pain: an experimental study in rats and β-common receptor knockout mice. Anesthesiology. 2011; 115(5):1084-92. DOI: 10.1097/ALN.0b013e31822fcefd. View

Hughes R . Systematic reviews of treatment for inflammatory demyelinating neuropathy. J Anat. 2002; 200(4):331-9. PMC: 1570692. DOI: 10.1046/j.1469-7580.2002.00041.x. View

Kiefer R, Kieseier B, Stoll G, Hartung H . The role of macrophages in immune-mediated damage to the peripheral nervous system. Prog Neurobiol. 2001; 64(2):109-27. DOI: 10.1016/s0301-0082(00)00060-5. View

Farrell F, Lee A . The erythropoietin receptor and its expression in tumor cells and other tissues. Oncologist. 2004; 9 Suppl 5:18-30. DOI: 10.1634/theoncologist.9-90005-18. View

Maiese K, Chong Z, Li F, Shang Y . Erythropoietin: elucidating new cellular targets that broaden therapeutic strategies. Prog Neurobiol. 2008; 85(2):194-213. PMC: 2441910. DOI: 10.1016/j.pneurobio.2008.02.002. View

Brines M, Patel N, Villa P, Brines C, Mennini T, De Paola M . Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin. Proc Natl Acad Sci U S A. 2008; 105(31):10925-30. PMC: 2504825. DOI: 10.1073/pnas.0805594105. View

Bohlius J, Weingart O, Trelle S, Engert A . Cancer-related anemia and recombinant human erythropoietin--an updated overview. Nat Clin Pract Oncol. 2006; 3(3):152-64. DOI: 10.1038/ncponc0451. View

10.

Dong C . TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat Rev Immunol. 2008; 8(5):337-48. DOI: 10.1038/nri2295. View

11.

Nairz M, Sonnweber T, Schroll A, Theurl I, Weiss G . The pleiotropic effects of erythropoietin in infection and inflammation. Microbes Infect. 2011; 14(3):238-46. PMC: 3278592. DOI: 10.1016/j.micinf.2011.10.005. View

12.

Schabet M, Whitaker J, Schott K, Stevens A, Zurn A, Buhler R . The use of protease inhibitors in experimental allergic neuritis. J Neuroimmunol. 1991; 31(3):265-72. DOI: 10.1016/0165-5728(91)90048-c. View

13.

Maurer M, Toyka K, Gold R . Cellular immunity in inflammatory autoimmune neuropathies. Rev Neurol (Paris). 2003; 158(12 Pt 2):S7-15. View

14.

Brines M, Grasso G, Fiordaliso F, Sfacteria A, Ghezzi P, Fratelli M . Erythropoietin mediates tissue protection through an erythropoietin and common beta-subunit heteroreceptor. Proc Natl Acad Sci U S A. 2004; 101(41):14907-12. PMC: 522054. DOI: 10.1073/pnas.0406491101. View

15.

Henke M, Laszig R, Rube C, Schafer U, Haase K, Schilcher B . Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial. Lancet. 2003; 362(9392):1255-60. DOI: 10.1016/S0140-6736(03)14567-9. View

16.

Rosenzweig M, Bender C, Lucke J, Yasko J, Brufsky A . The decision to prematurely terminate a trial of R-HuEPO due to thrombotic events. J Pain Symptom Manage. 2004; 27(2):185-90. DOI: 10.1016/j.jpainsymman.2003.06.010. View

17.

Chateauvieux S, Grigorakaki C, Morceau F, Dicato M, Diederich M . Erythropoietin, erythropoiesis and beyond. Biochem Pharmacol. 2011; 82(10):1291-303. DOI: 10.1016/j.bcp.2011.06.045. View

18.

Xanthos T, Vasileiou P, Kakavas S, Syggelou A, Iacovidou N . The potential role of erythropoietin as a pleiotropic agent in post-cardiac arrest syndrome. Curr Pharm Des. 2011; 17(15):1517-29. DOI: 10.2174/138161211796197115. View

19.

Brines M, Cerami A . Emerging biological roles for erythropoietin in the nervous system. Nat Rev Neurosci. 2005; 6(6):484-94. DOI: 10.1038/nrn1687. View

20.

Zhang Z, Zhang Z, Fauser U, Schluesener H . Distribution of Foxp3(+) T-regulatory cells in experimental autoimmune neuritis rats. Exp Neurol. 2008; 216(1):75-82. DOI: 10.1016/j.expneurol.2008.11.014. View