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LIGHT induces cell proliferation and inflammatory responses of rheumatoid arthritis synovial fibroblasts via lymphotoxin beta receptor.
- Source :
-
The Journal of rheumatology [J Rheumatol] 2008 Jun; Vol. 35 (6), pp. 960-8. Date of Electronic Publication: 2008 Apr 15. - Publication Year :
- 2008
-
Abstract
- Objective: To investigate the effects of LIGHT (lymphotoxin-like, exhibits inducible expression and competes with herpes simplex virus glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes) on the proliferation and gene expression of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA).<br />Methods: We measured LIGHT levels in RA synovial fluids (SF) by ELISA, and compared them with those in osteoarthritis (OA) SF. Levels of LIGHT and its receptors in RA-FLS and synovium were assessed using real-time quantitative polymerase chain reaction (PCR). RA-FLS proliferation was examined by a bromodeoxyuridine assay. Expression of intercellular adhesion molecule-1 (ICAM-1) and several chemokines, such as interleukin 8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1alpha (MIP-1alpha), was examined by real-time quantitative PCR, ELISA, and flow cytometry. The effects of LIGHT on nuclear factor-kappaB (NF-kappaB) activation were investigated using immunofluorescence and Western blotting.<br />Results: LIGHT was upregulated in both SF and synovium of RA patients compared with OA patients. Herpes virus entry mediator (HVEM) and lymphotoxin beta receptor (LTbetaR), but not LIGHT, were detected in RA-FLS. LIGHT significantly promoted RA-FLS proliferation and induced expression of MCP-1, IL-8, MIP-1alpha, and ICAM-1 by RA-FLS. As well, LTbetaR small interfering RNA (siRNA), but not HVEM siRNA, inhibited these effects of LIGHT. LIGHT induced IkappaBa degradation and NF-kappaB translocation, and a NF-kappaB inhibitor suppressed the effects of LIGHT on RA-FLS.<br />Conclusion: Our findings suggest that LIGHT signaling via LTbetaR plays an important role in the pathogenesis of RA by affecting key processes such as the proliferation and activation of RA-FLS. Regulation of LIGHT-LTbetaR signaling may represent a new therapeutic target for RA treatment.
- Subjects :
- Adult
Aged
Aged, 80 and over
Cell Proliferation
Cells, Cultured
Female
Fibroblasts
Humans
Middle Aged
Osteoarthritis metabolism
Receptors, Tumor Necrosis Factor, Member 14 metabolism
Signal Transduction
Synovial Fluid cytology
Synovial Membrane cytology
Up-Regulation
Arthritis, Rheumatoid metabolism
Lymphotoxin beta Receptor metabolism
Synovial Fluid metabolism
Synovial Membrane metabolism
Tumor Necrosis Factor Ligand Superfamily Member 14 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0315-162X
- Volume :
- 35
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Journal of rheumatology
- Publication Type :
- Academic Journal
- Accession number :
- 18412315