| LIGHT up-regulated on B lymphocytes and monocytes in rheumatoid arthritis mediates cellular adhesion and metalloproteinase production by synoviocytes. | |
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MedLine Citation:
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PMID: 17393389 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: To study the expression of LIGHT (tumor necrosis factor superfamily 14) and herpesvirus entry mediator (HVEM; tumor necrosis factor receptor superfamily 14) in rheumatoid arthritis (RA) and to determine the regulatory role of LIGHT on the effector functions of fibroblast-like synoviocytes (FLS). METHODS: The expression of LIGHT and HVEM was assessed by immunohistochemical staining of synovial tissue and by flow cytometric analysis of mononuclear cells. The presence of HVEM and lymphotoxin beta receptor was measured by reverse transcriptase-polymerase chain reaction and by flow cytometry. The regulation of effector molecules, including matrix metalloproteinases (MMPs) and adhesion molecules, was evaluated. The adhesiveness of FLS was determined by adhesion assay. RESULTS: HVEM was detected in most cell types within rheumatoid synovial tissue, while only a few cells were positive for LIGHT. In RA patients, LIGHT expression was significantly up-regulated only in CD20+ B cells and monocytes, whereas the mean fluorescence intensity of HVEM was down-regulated in mononuclear cells. The stimulation of FLS with LIGHT resulted in the production of MMPs and the expression of adhesion molecules, which were efficiently inhibited by dexamethasone. LIGHT-mediated up-regulation of MMPs and intercellular adhesion molecule 1 was blocked by inhibitors of NF-kappaB and JNK, whereas up-regulation of vascular cell adhesion molecule 1 was blocked by inhibitors of phosphatidylinositol 3-kinase, as well as NF-kappaB. CONCLUSION: These data suggest that binding of LIGHT with its receptors may play a role in the progression of inflammation within rheumatoid synovium, especially by mediating the interactions between infiltrating inflammatory cells and stromal cells. These findings thus emphasize the relevance of LIGHT as a potential therapeutic target in RA. |
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Authors:
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Young Mo Kang; So Young Kim; Jin Hee Kang; Seung Woo Han; Eon Jeong Nam; Hee Soo Kyung; Jae Yong Park; In San Kim |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Arthritis and rheumatism Volume: 56 ISSN: 0004-3591 ISO Abbreviation: Arthritis Rheum. Publication Date: 2007 Apr |
Date Detail:
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Created Date: 2007-04-19 Completed Date: 2007-05-10 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370605 Medline TA: Arthritis Rheum Country: United States |
Other Details:
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Languages: eng Pagination: 1106-17 Citation Subset: AIM; IM |
Affiliation:
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Kyungpook National University School of Medicine, and Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea. ymkang@knu.ac.kr |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Arthritis, Rheumatoid / metabolism* B-Lymphocytes / metabolism*, pathology Cell Adhesion / genetics Female Fibroblasts / enzymology, pathology Flow Cytometry Fluorescent Antibody Technique, Indirect Humans Male Metalloproteases / genetics, metabolism* Middle Aged Monocytes / metabolism*, pathology Osteoarthritis / metabolism* RNA, Messenger / metabolism Receptors, Tumor Necrosis Factor, Member 14 / genetics, metabolism Synovial Membrane / enzymology*, pathology Synovitis / metabolism, pathology Tumor Necrosis Factor Ligand Superfamily Member 14 / genetics, metabolism* Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; 0/Receptors, Tumor Necrosis Factor, Member 14; 0/TNFRSF14 protein, human; 0/TNFSF14 protein, human; 0/Tumor Necrosis Factor Ligand Superfamily Member 14; EC 3.4.-/Metalloproteases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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