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Inflammation Research

Erschienen in:

01.09.2011 | Original Research Paper

Inhibition of inflammatory mediators and related signaling pathways by macrophage-stimulating protein in rheumatoid arthritis synovial fibroblasts

verfasst von: Xiang-min Tong, Jian-chao Wang, Yuedi shen, Jun-jun Xie, Jun-yu Zhang, Jie Jin

Erschienen in: Inflammation Research | Ausgabe 9/2011

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Abstract

Objective

To evaluate the mechanism of macrophage-stimulating protein (MSP)-mediated inhibition of inflammatory cytokine and chemokine production in rheumatoid arthritis synovial fibroblasts (RASF).

Materials and methods

RASF were treated with different concentrations (0, 0.5, 1, 5 and 10 ng/ml) of MSP with or without 1 μg/mL lipopolysaccharide (LPS). The protein expressions of IL-1β, TNF-α, IL-18, MIP-1, MCP-1, RANTES and PGE₂ were analyzed by enzyme-linked immunosorbent assays (ELISA). The total nitric oxide (NO) concentration was determined using the Griess reaction. The protein expressions of iNOS, COX-2, NF-κB(p-p65), IKB-α, IKB-β, p-P38, p-Erk1/2 (P-P42/44) and p-AKT were detected by Western blotting.

Results

MSP markedly inhibited expression of inflammatory cytokines (IL-1β, TNF-α and IL-18), chemokines (MIP-1, MCP-1 and RANTES) and iNOS, NO, COX-2 and PGE₂ in RASF stimulated by LPS. MSP treatment decreased expressions of p-IκBα, p-IKBβ and p-P65 in RASF in a concentration-dependent manner. Expressions of p-AKT, p-p38 and p-Erk1/2 were also inhibited markedly in RASF stimulated by LPS after treatment with MSP in a concentration-dependent manner.

Conclusion

MSP could inhibit the inflammatory cycle by suppressing inflammatory mediators and activation of NF-κB as well. The inhibitory effect of MSP on LPS-stimulated RASF may act through suppression of multiple signals such as the PI3K/AKT and/or MAPK pathways.

Cox JH, Starr AE, Kappelhoff R, Yan R, Roberts CR. Overall CM.Matrix metalloproteinase 8 deficiency in mice exacerbates inflammatory arthritis through delayed neutrophil apoptosis and reduced caspase 11 expression. Arthritis Rheum. 2010;62(12):3645–55.PubMedCrossRef

Firestein GS. Evolving concepts of rheumatoid arthritis. Nature. 2003;423(6937):356–61.PubMedCrossRef

Steiner G. Auto-antibodies and autoreactive T-cells in rheumatoid arthritis: pathogenetic players and diagnostic tools. Clin Rev Allergy Immunol. 2007;32(1):23–36.PubMedCrossRef

Tas SW, Remans PH, Reedquist KA, Tak PP. Signal transduction pathway and transcription factors as therapeutic targets in inflammatory disease: towards innovative anti-rheumatic therapy. Curr Pharm Des. 2005;11(5):581–611.PubMedCrossRef

Jüngel A, Distler O, Schulze-Horsel U, Huber LC, Ha HR, Simmen B, Kalden JR, Pisetsky DS, Gay S, Distler JH. Microparticles stimulate the synthesis of prostaglandin E(2) via induction of cyclooxygenase 2 and microsomal prostaglandin E synthase 1. Arthritis Rheum. 2007;56(11):3564–74.PubMedCrossRef

Suzuki Y, Funakoshi H, Machide M, Matsumoto K, Nakamura T. Regulation of cell migration and cytokine production by HGF-like protein (HLP)/macrophage stimulating protein (MSP) in primary microglia. Biomed Res. 2008;29(2):77–84.PubMedCrossRef

Wang MH, Zhou YQ, Chen YQ. Macrophage-stimulating protein and RON receptor tyrosine kinase: potential regulators of macrophage inflammatory activities. Scand J Immunol. 2002;56(6):545–53.PubMedCrossRef

Yao HP, Qian Y, Shao XT, Xu ZR, Cheng LF, Feng L, Wu NP, Yang YM. Construction of a recombinant adenovirus vector expressing IL-18BP/IL-4 fusion gene and the anti-inflammatory effect induced by this gene on lipopolysaccharide- stimulated synovial fibroblasts. Inflamm Res. 2010;59(2):97–104.PubMedCrossRef

Wang A, Guilpain P, Chong BF, Chouzenoux S, Guillevin L, Du Y, Zhou XJ, Lin F, Fairhurst AM, Boudreaux C, Roux C, Wakeland EK, Davis LS, Batteux F, Mohan C. Dysregulated expression of CXCR4/CXCL12 in subsets of patients with systemic lupus erythematosus. Arthritis Rheum. 2010;62(11):3436–46.PubMedCrossRef

10.

Park JY, Pillinger MH, Abramson SB. Prostaglandin E2 synthesis and secretion: the role of PGE2 synthases. Clin Immunol. 2006;119(3):229–40.PubMedCrossRef

11.

Bartok B, Firestein GS. Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunol Rev. 2010;233(1):233–55.PubMedCrossRef

12.

Zhou YQ, Chen YQ, Fisher JH, et al. Activation of the RON receptor tyrosine kinase by macrophage-stimulating protein inhibits inducible cyclooxygenase-2 expression in murine macrophages. J Biol Chem. 2002;277(41):38104–10.PubMedCrossRef

13.

Capria A, De Nardo D, Baffetti FR, Barbini U, Violo A, Tondo T, Fontana L. Long-term anti-TNF-alpha treatments reverse the endothelial dysfunction in rheumatoid arthritis: the biological coherence between synovial and endothelial inflammation. Int J Immunopathol Pharmacol. 2010;23(1):255–62.PubMed

14.

Zhang HG, Wang Y, Xie JF, Liang X, Liu D, Yang P, et al. Regulation of tumor necrosis factor alpha-mediated apoptosis of rheumatoid arthritis synovial fibroblasts by the protein kinase Akt. Arthritis Rheum. 2001;44(7):1555–67.PubMedCrossRef

15.

Pap T, Franz JK, Hummel KM, Jeisy E, Gay R, Gay S. Activation of synovial fibroblasts in rheumatoid arthritis: lack of expression of the tumour suppressor PTEN at sites of invasive growth and destruction. Arthritis Res. 2000;2(1):59–64.PubMedCrossRef

16.

Pahan K, Raymond JR, Singh I. Inhibition of phosphatidylinositol 3-kinase induces nitric-oxide synthase in lipopolysaccharide- or cytokine-stimulated C6 glial cells. J Biol Chem. 1999;274(11):7528–36.PubMedCrossRef

17.

Schett G, Tohidast-Akrad M, Smolen JS, Schmid BJ, Steiner CW, Bitzan P. Activation, differential localization, and regulation of the stress-activated protein kinases, extracellular signal-regulated kinase, c-JUN N-terminal kinase, and p38 mitogen-activated protein kinase, in synovial tissue and cells in rheumatoid arthritis. Arthritis Rheum. 2000;43(11):2501–12.PubMedCrossRef

18.

Choi EM, Lee YS. Luteolin suppresses IL-1beta-induced cytokines and MMPs production via p38 MAPK, JNK, NF-kappaB and AP-1 activation in human synovial sarcoma cell line, SW982. Food Chem Toxicol. 2010;48(10):2607–11.PubMedCrossRef

19.

Page TH, Brown A, Timms EM, Foxwell BM, Ray KP. Inhibitors of p38 suppress cytokine production in rheumatoid arthritis synovial membranes: does variable inhibition of interleukin-6 production limit effectiveness in vivo? Arthritis Rheum. 2010;62(11):3221–31.PubMedCrossRef

20.

Bae EM, Kim WJ, Suk K, Kang YM, Park JE, Kim WY, Choi EM, Choi BK, Kwon BS, Lee WH. Reverse signaling initiated from GITRL induces NF-kappaB activation through ERK in the inflammatory activation of macrophages. Mol Immunol. 2008;45(2):523–33.PubMedCrossRef

21.

Kunisch E, Gandesiri M, Fuhrmann R, Roth A, Winter R, Kinne RW. Predominant activation of MAP kinases and pro-destructive/pro-inflammatory features by TNF alpha in early-passage synovial fibroblasts via TNF receptor-1: failure of p38 inhibition to suppress matrix metalloproteinase-1 in rheumatoid arthritis. Ann Rheum Dis. 2007;66(8):1043–51.PubMedCrossRef

Titel: Inhibition of inflammatory mediators and related signaling pathways by macrophage-stimulating protein in rheumatoid arthritis synovial fibroblasts
verfasst von: Xiang-min Tong
Jian-chao Wang
Yuedi shen
Jun-jun Xie
Jun-yu Zhang
Jie Jin
Publikationsdatum: 01.09.2011
Verlag: SP Birkhäuser Verlag Basel
Erschienen in: Inflammation Research / Ausgabe 9/2011
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-011-0338-1

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