LIGHT induces cell proliferation and inflammatory responses of rheumatoid arthritis synovial fibroblasts via lymphotoxin β receptor

Satoru Ishida, Shoji Yamane, Saori Nakano, Toshihito Mori, Takuo Juji, Naoshi Fukui, Tsunetoshi Itoh, Takahiro Ochi, Ryuji Suzuki

研究成果: Article査読

22 被引用数 (Scopus)

抄録

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 β receptor (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 IαBa 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.

本文言語English
ページ(範囲)960-968
ページ数9
ジャーナルJournal of Rheumatology
35
6
出版ステータスPublished - 2008 6 1

ASJC Scopus subject areas

  • リウマチ学
  • 免疫アレルギー学
  • 免疫学

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