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LIGHT up-regulated on B lymphocytes and monocytes in rheumatoid arthritis mediates cellular adhesion and metalloproteinase production by synoviocytes.

AbstractOBJECTIVE:
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.
AuthorsYoung Mo Kang, So Young Kim, Jin Hee Kang, Seung Woo Han, Eon Jeong Nam, Hee Soo Kyung, Jae Yong Park, In San Kim
JournalArthritis and rheumatism (Arthritis Rheum) Vol. 56 Issue 4 Pg. 1106-17 (Apr 2007) ISSN: 0004-3591 [Print] United States
PMID17393389 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • RNA, Messenger
  • Receptors, Tumor Necrosis Factor, Member 14
  • TNFRSF14 protein, human
  • TNFSF14 protein, human
  • Tumor Necrosis Factor Ligand Superfamily Member 14
  • Metalloproteases
Topics
  • 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

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