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J Cell Mol Med. 2017 Mar;21(3):475-486. doi: 10.1111/jcmm.12991. Epub 2016 Sep 28.

Inhibition of cytokine response to TLR stimulation and alleviation of collagen-induced arthritis in mice by Schistosoma japonicum peptide SJMHE1.

Wang X1,2, Li L1,2, Wang J3, Dong L1,2, Shu Y1,2, Liang Y4, Shi L1,2, Xu C1,2, Zhou Y1,2, Wang Y1, Chen D1,2, Mao C1,2.

Author information

1
Department of Central Laboratory, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.
2
Department of Nuclear Medicine and Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.
3
Department of Nuclear Medicine, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
4
Clinical Laboratory, Huai'an Hospital Affiliated of Xuzhou Medical College, Huaian, Jiangsu, China.

Abstract

Helminth-derived products have recently been shown to prevent the development of inflammatory diseases in mouse models. However, most identified immunomodulators from helminthes are mixtures or macromolecules with potentially immunogenic side effects. We previously identified an immunomodulatory peptide called SJMHE1 from the HSP60 protein of Schistosoma japonicum. In this study, we assessed the ability of SJMHE1 to affect murine splenocytes and human peripheral blood mononuclear cells (PBMCs) stimulated by toll-like receptor (TLR) ligands in vitro and its treatment effect on mice with collagen-induced arthritis (CIA). We show that SJMHE1 not only modulates the cytokine production of murine macrophage (MΦ) and dendritic cell but also affects cytokine production upon coculturing with allogeneic CD4+ T cell. SJMHE1 potently inhibits the cytokine response to TLR ligands lipopolysaccharide (LPS), CpG oligodeoxynucleotides (CpG) or resiquimod (R848) from mouse splenocytes, and human PBMCs stimulated by LPS. Furthermore, SJMHE1 suppressed clinical signs of CIA in mice and blocked joint erosion progression. This effect was mediated by downregulation of key cytokines involved in the pathogenesis of CIA, such as interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), interleukin (IL)-6, IL-17, and IL-22 and up-regulation of the inhibitory cytokine IL-10, Tgf-β1 mRNA, and CD4+ CD25+ Foxp3+ Tregs. This study provides new evidence that the peptide from S. japonicum, which is the 'safe' selective generation of small molecule peptide that has evolved during host-parasite interactions, is of great value in the search for novel anti-inflammatory agents and therapeutic targets for autoimmune diseases.

KEYWORDS:

Schistosoma japonicum peptide SJMHE1; alleviation; collagen-induced arthritis; cytokine response; inhibition; toll-like receptor

PMID:
27677654
PMCID:
PMC5323857
DOI:
10.1111/jcmm.12991
[Indexed for MEDLINE]
Free PMC Article

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