LIGHT is Involved in the Pathogenesis of Rheumatoid Arthritis by Inducing the Expression of Pro-inflammatory Cytokines and MMP-9 in Macrophages

Overview

Journal Immunology

Specialty Allergy & Immunology

Date 2005 Jan 26

PMID 15667572

Citations 24

Authors

Won-Jung Kim

Yoon-Joong Kang

Eun-Mi Koh

Kwang-Sung Ahn

Hoon-Suk Cha

Won-Ha Lee

Affiliations

Soon will be listed here.

Abstract

Macrophages play a crucial role in the perpetuation of inflammation and irreversible cartilage damage during the development of rheumatoid arthritis (RA). LIGHT (TNFSF14) and its receptor TR2 (TNFRSF14) are known to have pro-inflammatory activities in foam cells of atherosclerotic plaques. We tested a hypothesis that LIGHT and TR2 are involved in activation of monocyte/macrophages in RA synovium. Immunohistochemical analysis of RA synovial tissue samples revealed that both LIGHT and TR2 are expressed in CD68 positive macrophages. In contrast, synovial tissue samples from osteoarthritis (OA) patients failed to reveal the expression of LIGHT. Expression of TR2 in RA synovial macrophages was also detected using flow cytometry analysis. To identify the role of LIGHT in the functioning of macrophages in RA, we isolated macrophage enriched cells from RA synovial fluid and stimulated them with LIGHT. LIGHT induced expression of matrix metalloproteinase-9 and pro-inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8. These data indicate that LIGHT and TR2 expressed in macrophages are involved in the pathogenesis of RA by inducing the expression pro-inflammatory cytokines and matrix degrading enzymes.

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References

Lee W, Lee Y, Kim J, Chu J, Lee S, Jung J . Activation of monocytes, T-lymphocytes and plasma inflammatory markers in angina patients. Exp Mol Med. 1999; 31(3):159-64. View

Bresnihan B . Pathogenesis of joint damage in rheumatoid arthritis. J Rheumatol. 1999; 26(3):717-9. View

Kinne R, Brauer R, Stuhlmuller B, Palombo-Kinne E, Burmester G . Macrophages in rheumatoid arthritis. Arthritis Res. 2000; 2(3):189-202. PMC: 130001. DOI: 10.1186/ar86. View

Lubberts E, Joosten L, Oppers B, van den Bersselaar L, Kolls J, Schwarzenberger P . IL-1-independent role of IL-17 in synovial inflammation and joint destruction during collagen-induced arthritis. J Immunol. 2001; 167(2):1004-13. DOI: 10.4049/jimmunol.167.2.1004. View

Lee W, Kim S, Lee Y, Lee B, Kwon B, Song H . Tumor necrosis factor receptor superfamily 14 is involved in atherogenesis by inducing proinflammatory cytokines and matrix metalloproteinases. Arterioscler Thromb Vasc Biol. 2001; 21(12):2004-10. DOI: 10.1161/hq1201.098945. View

Romas E, Gillespie M, Martin T . Involvement of receptor activator of NFkappaB ligand and tumor necrosis factor-alpha in bone destruction in rheumatoid arthritis. Bone. 2002; 30(2):340-6. DOI: 10.1016/s8756-3282(01)00682-2. View

Ye Q, Fraser C, Gao W, Wang L, Busfield S, Wang C . Modulation of LIGHT-HVEM costimulation prolongs cardiac allograft survival. J Exp Med. 2002; 195(6):795-800. PMC: 2193745. DOI: 10.1084/jem.20012088. View

Vervoordeldonk M, Tak P . Cytokines in rheumatoid arthritis. Curr Rheumatol Rep. 2002; 4(3):208-17. DOI: 10.1007/s11926-002-0067-0. View

Scheu S, Alferink J, Potzel T, Barchet W, Kalinke U, Pfeffer K . Targeted disruption of LIGHT causes defects in costimulatory T cell activation and reveals cooperation with lymphotoxin beta in mesenteric lymph node genesis. J Exp Med. 2002; 195(12):1613-24. PMC: 2193565. DOI: 10.1084/jem.20020215. View

10.

Wang J, Foster A, Chin R, Yu P, Sun Y, Wang Y . The complementation of lymphotoxin deficiency with LIGHT, a newly discovered TNF family member, for the restoration of secondary lymphoid structure and function. Eur J Immunol. 2002; 32(7):1969-79. DOI: 10.1002/1521-4141(200207)32:7<1969::AID-IMMU1969>3.0.CO;2-M. View

11.

Dayer J . Interleukin 1 or tumor necrosis factor-alpha: which is the real target in rheumatoid arthritis?. J Rheumatol Suppl. 2002; 65:10-5. View

12.

Shi G, Luo H, Wan X, Salcedo T, Zhang J, Wu J . Mouse T cells receive costimulatory signals from LIGHT, a TNF family member. Blood. 2002; 100(9):3279-86. DOI: 10.1182/blood-2002-05-1404. View

13.

Wan X, Zhang J, Luo H, Shi G, Kapnik E, Kim S . A TNF family member LIGHT transduces costimulatory signals into human T cells. J Immunol. 2002; 169(12):6813-21. DOI: 10.4049/jimmunol.169.12.6813. View

14.

Firestein G . Evolving concepts of rheumatoid arthritis. Nature. 2003; 423(6937):356-61. DOI: 10.1038/nature01661. View

15.

Fava R, Notidis E, Hunt J, Szanya V, Ratcliffe N, Ngam-ek A . A role for the lymphotoxin/LIGHT axis in the pathogenesis of murine collagen-induced arthritis. J Immunol. 2003; 171(1):115-26. DOI: 10.4049/jimmunol.171.1.115. View

16.

Rubbert-Roth A, Perniok A . [Interleukin-1 receptor antagonist anakinra (Kineret) for treatment of rheumatic arthritis]. Z Rheumatol. 2003; 62(4):367-77. DOI: 10.1007/s00393-003-0545-4. View

17.

Jung H, La S, Kim J, Heo S, Kim J, Wang S . High levels of soluble herpes virus entry mediator in sera of patients with allergic and autoimmune diseases. Exp Mol Med. 2004; 35(6):501-8. DOI: 10.1038/emm.2003.65. View

18.

Moon S, Cha B, Kim C . ERK1/2 mediates TNF-alpha-induced matrix metalloproteinase-9 expression in human vascular smooth muscle cells via the regulation of NF-kappaB and AP-1: Involvement of the ras dependent pathway. J Cell Physiol. 2004; 198(3):417-27. DOI: 10.1002/jcp.10435. View

19.

Bang L, Keating G . Adalimumab: a review of its use in rheumatoid arthritis. BioDrugs. 2004; 18(2):121-39. DOI: 10.2165/00063030-200418020-00005. View

20.

Giannelli G, Erriquez R, Iannone F, Marinosci F, Lapadula G, Antonaci S . MMP-2, MMP-9, TIMP-1 and TIMP-2 levels in patients with rheumatoid arthritis and psoriatic arthritis. Clin Exp Rheumatol. 2004; 22(3):335-8. View