Non-erythropoietic erythropoietin-derived peptide protects mice from systemic lupus erythematosus.

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease, which results in various organ pathologies. However, current treatment towards SLE is suboptimal. Erythropoietin (EPO) has been shown to promote SLE recovery, but clinical application can be limited by its haematopoiesis-stimulating effects. EPO-derived helix-B peptide (ARA290) is non-erythrogenic but has been reported to retain the anti-inflammatory and tissue-protective functions of EPO. Therefore, here we investigated the effects and potential mechanisms of ARA290 on SLE. The administration of ARA290 to pristane-induced SLE and MRL/lpr mice significantly suppressed the level of serum antinuclear autoantibodies (ANAs) and anti-dsDNA autoantibodies, reduced the deposition of IgG and C3, and ameliorated the nephritis symptoms. Moreover, the serum concentrations of inflammatory cytokine IL-6, MCP-1 and TNF-α in SLE mice were reduced by ARA290. Further, ARA290 decreased the number of apoptotic cells in kidney. In vitro experiment revealed that ARA290 inhibited the inflammatory activation of macrophages and promoted the phagocytotic function of macrophages to apoptotic cells. Finally, ARA290 did not induce haematopoiesis during treatment. In conclusion, ARA290 ameliorated SLE, which at least could be partly due to its anti-inflammatory and apoptotic cell clearance promoting effects, without stimulating haematopoiesis, suggesting that ARA290 could be a hopeful candidate for SLE treatment.

• Authors: Bo Huang, Juntao Jiang, Bangwei Luo, Wen Zhu, Yuqi Liu, Zhishang Wang, Zhiren Zhang
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 22 Issue 7 Pg. 3330-3339 (07 2018) ISSN: 1582-4934 [Electronic] England
• PMID: 29570934 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• Cytokines
• Oligopeptides
• Terpenes
• Erythropoietin
• pristane
• cibinetide

Topics

• Animals
• Cytokines (blood)
• Disease Models, Animal
• Erythropoietin (chemistry)
• Female
• Hematopoiesis (drug effects)
• Inflammation (drug therapy, etiology)
• Kidney (drug effects, pathology)
• Lupus Erythematosus, Systemic (chemically induced, drug therapy, pathology)
• Macrophage Activation (drug effects)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred MRL lpr
• Oligopeptides (pharmacology)
• Phagocytosis (drug effects)
• RAW 264.7 Cells
• Terpenes (toxicity)