RT Journal Article
SR Electronic
T1 LIGHT Induces Cell Proliferation and Inflammatory Responses of Rheumatoid Arthritis Synovial Fibroblasts via Lymphotoxin β Receptor
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 960
OP 968
VO 35
IS 6
A1 SATORU ISHIDA
A1 SHOJI YAMANE
A1 SAORI NAKANO
A1 TOSHIHITO MORI
A1 TAKUO JUJI
A1 NAOSHI FUKUI
A1 TSUNETOSHI ITOH
A1 TAKAHIRO OCHI
A1 RYUJI SUZUKI
YR 2008
UL http://www.jrheum.org/content/35/6/960.abstract
AB 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). 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-1α (MIP-1α), was examined by real-time quantitative PCR, ELISA, and flow cytometry. The effects of LIGHT on nuclear factor-κB (NF-κB) activation were investigated using immunofluorescence and Western blotting. Results LIGHT was upregulated in both SF and synovium of RA patients compared with OA patients. Herpes virus entry mediator (HVEM) and lymphotoxin βreceptor (LTβR), but not LIGHT, were detected in RA-FLS. LIGHT significantly promoted RA-FLS proliferation and induced expression of MCP-1, IL-8, MIP-1α, and ICAM-1 by RA-FLS. As well, LTβR small interfering RNA (siRNA), but not HVEM siRNA, inhibited these effects of LIGHT. LIGHT induced IκBa degradation and NF-κB translocation, and a NF-κB inhibitor suppressed the effects of LIGHT on RA-FLS. Conclusion Our findings suggest that LIGHT signaling via LTβR 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-LTβR signaling may represent a new therapeutic target for RA treatment.