ORIGINAL ARTICLE

Thymic stromal lymphopoietin secretion of synovial fibroblasts is positively and negatively regulated by Toll-like receptors/nuclear factor-κB pathway and interferon-γ/dexamethasone

Authors

Tetsuro Ozawa¹, Kensuke Koyama^1,2, Takashi Ando¹, Yuko Ohnuma¹, Kyosuke Hatsushika¹, Tetsuro Ohba^1,2, Hajime Sugiyama², Yoshiki Hamada², Hideoki Ogawa³, Ko Okumura³ and Atsuhito Nakao^1,3

1. Department of Immunology, Faculty of Medicine, University of Yamanashi, Chuo, Japan
2. Department of Orthopaedic Surgery, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo 409-3898, Japan
3. Atopy Research Center, Juntendo University School of Medicine, Tokyo, Japan

Received:

13 April 2007

Accepted:

14 June 2007

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Abstract

Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine produced by epithelial cells and triggers dendritic cell-mediated Th2 type allergic inflammatory responses. This study investigated whether Toll-like receptor (TLR) ligands, lipopolysaccharide (LPS) and poly-IC affect TSLP production in synovial fibroblasts. Enzyme-linked immunosorbent assay showed that LPS and poly-IC upregulated TSLP production in synovial fibroblasts obtained from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). In addition, we found that nuclear factor (NF)-κB inhibitor IMD-0354, dexamethasone, and interferon (IFN)-γ inhibited the LPS- and poly-IC-induced TSLP production in RA and OA synovial fibroblasts. Thus, LPS and poly-IC can upregulate TSLP via a NF-κB pathway in synovial fibroblasts, which is downregulated by dexamethasone and interferon (IFN)-γ. The current findings suggest that TSLP may be involved in the pathophysiology of inflammatory arthritis as well as allergic disease.

Key words

Nuclear factor-κB - Rheumatoid arthritis - Synovial fibroblasts - Thymic stromal lymphopoietin (TSLP) - Toll-like receptor ligands