Inhibition of cytokine response to TLR stimulation and alleviation of collagen-induced arthritis in mice by Schistosoma japonicum peptide SJMHE1.
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.
Department of Central Laboratory, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.|Department of Nuclear Medicine and Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Xuefeng
X
Wang
Department of Central Laboratory, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.|Department of Nuclear Medicine and Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Li
L
Li
Department of Nuclear Medicine, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
Jun
J
Wang
Department of Central Laboratory, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.|Department of Nuclear Medicine and Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Liyang
L
Dong
Department of Central Laboratory, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.|Department of Nuclear Medicine and Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Yang
Y
Shu
Clinical Laboratory, Huai'an Hospital Affiliated of Xuzhou Medical College, Huaian, Jiangsu, China.
Yong
Y
Liang
Department of Central Laboratory, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.|Department of Nuclear Medicine and Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Liang
L
Shi
Department of Central Laboratory, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.|Department of Nuclear Medicine and Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Chengcheng
C
Xu
Department of Central Laboratory, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.|Department of Nuclear Medicine and Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Yuepeng
Y
Zhou
Department of Central Laboratory, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Yi
Y
Wang
Department of Central Laboratory, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.|Department of Nuclear Medicine and Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Deyu
D
Chen
Department of Central Laboratory, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.|Department of Nuclear Medicine and Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Chaoming
C
Mao
D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced* / Q000188:drug therapy*; D001327:Autoimmune Diseases / Q000188:drug therapy; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D015801:Helminth Proteins / Q000494:pharmacology; D006790:Host-Parasite Interactions / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D051379:Mice; D010455:Peptides / Q000494:pharmacology*; D012549:Schistosoma japonicum / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D016207:Cytokines; D015801:Helminth Proteins; D010455:Peptides; D051193:Toll-Like Receptors; D003094:Collagen
Schistosoma japonicum peptide SJMHE1; alleviation; collagen-induced arthritis; cytokine response; inhibition; toll-like receptor
Curr Opin Immunol. 2004 Dec;16(6):695-701
15511660
Int J Rheum Dis. 2013 Jun;16(3):243-53
23981743
Eur J Immunol. 2009 Nov;39(11):3052-65
19882655
Mod Rheumatol. 2009;19(6):581-9
19697097
Immunol Rev. 2009 Jan;227(1):234-47
19120488
Proc Natl Acad Sci U S A. 2004 Oct 5;101 Suppl 2:14586-92
15308777
Immunol Rev. 2004 Oct;201:89-116
15361235
Front Immunol. 2012 Feb 01;3:8
22566894
PLoS Negl Trop Dis. 2013 Apr 04;7(4):e2164
23593527
J Med Econ. 2012;15(4):635-43
22332705
Discov Med. 2011 May;11(60):413-24
21616040
JAMA. 2006 May 17;295(19):2275-85
16705109
Eur J Immunol. 2007 Jul;37(7):1887-904
17563917
Nat Rev Immunol. 2010 Apr;10(4):278-84
20224568
Arthritis Rheum. 2013 Apr;65(4):960-71
23334981
Autoimmun Rev. 2014 Jun;13(6):615-20
24418299
PLoS Negl Trop Dis. 2013;7(3):e2136
23556020
Joint Bone Spine. 2011 May;78(3):230-4
20961791
BioDrugs. 2009;23 (2):111-24
19489652
PLoS Negl Trop Dis. 2010 Apr 20;4(4):e667
20422029
Parasite Immunol. 2007 Mar;29(3):127-37
17266740
J Autoimmun. 2012 Sep;39(3):222-8
22704962
Parasit Vectors. 2016 Mar 12;9:147
26971312
J Immunol. 2004 Dec 15;173(12):7454-61
15585871
Mol Immunol. 2007 Apr;44(10):2605-15
17241663
Infect Immun. 2009 Mar;77(3):1144-54
19124604
Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2918-21
2011600
J Biol Chem. 2003 Jan 3;278(1):174-9
12403778
Autoimmun Rev. 2007 Nov;7(1):65-70
17967728
Nat Med. 2005 Apr;11(4 Suppl):S69-76
15812493
Curr Gene Ther. 2009 Aug;9(4):306-15
19534651
Arthritis Rheumatol. 2014 Nov;66(11):3083-95
25047518
J Immunol. 2009 Jul 1;183(1):191-200
19542430
Parasite Immunol. 1999 Apr;21(4):169-76
10320614
Eur J Immunol. 2011 Sep;41(9):2709-18
21710488
Arthritis Rheum. 2012 Oct;64(10):3068-71
22886766
BMC Med. 2015 Apr 13;13:81
25879741
J Neuroimmunol. 2008 Feb;194(1-2):107-14
18207251
Front Immunol. 2013 Aug 28;4:240
24009607
Front Immunol. 2013 Feb 20;4:39
23429492
Drugs. 2000 Jun;59(6):1341-59
10882166
Nat Rev Immunol. 2005 May;5(5):420-6
15864275
J Exp Med. 2005 Mar 21;201(6):949-60
15781585
Curr Opin Rheumatol. 2010 May;22(3):307-15
20090526
Arthritis. 2011;2011:765624
22046525
Rheumatology (Oxford). 2008 Jan;47(1):8-12
17715172
Nat Rev Immunol. 2007 Jun;7(6):429-42
17525752
Mol Immunol. 2012 Jun;51(2):210-8
22482518
Arthritis Rheum. 2002 Nov;46(11):3065-75
12428251
J Biol Chem. 2002 Dec 13;277(50):48122-9
12359728
J Cell Mol Med. 2014 Nov;18(11):2213-24
25164131
PLoS One. 2012;7(7):e40359
22802961
Arthritis Res Ther. 2010;12(4):214
20735862