Ozawa Tetsuro, Koyama Kensuke, Ando Takashi, Ohnuma Yuko, Hatsushika Kyosuke, Ohba Tetsuro, Sugiyama Hajime, Hamada Yoshiki, Ogawa Hideoki, Okumura Ko, Nakao Atsuhito
Department of Immunology, Faculty of Medicine, University of Yamanashi, Chuo, Japan.
Mod Rheumatol. 2007;17(6):459-63. doi: 10.1007/s10165-007-0620-9. Epub 2007 Dec 20.
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)-kappaB inhibitor IMD-0354, dexamethasone, and interferon (IFN)-gamma 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-kappaB pathway in synovial fibroblasts, which is downregulated by dexamethasone and interferon (IFN)-gamma. The current findings suggest that TSLP may be involved in the pathophysiology of inflammatory arthritis as well as allergic disease.
胸腺基质淋巴细胞生成素（TSLP）是一种由上皮细胞产生的白细胞介素（IL）-7样细胞因子，可触发树突状细胞介导的Th2型过敏性炎症反应。本研究调查了Toll样受体（TLR）配体、脂多糖（LPS）和聚肌苷酸-聚胞苷酸（poly-IC）是否影响滑膜成纤维细胞中TSLP的产生。酶联免疫吸附测定表明，LPS和poly-IC上调了类风湿性关节炎（RA）和骨关节炎（OA）患者滑膜成纤维细胞中TSLP的产生。此外，我们发现核因子（NF）-κB抑制剂IMD-0354、地塞米松和干扰素（IFN）-γ抑制RA和OA滑膜成纤维细胞中LPS和poly-IC诱导的TSLP产生。因此，LPS和poly-IC可通过滑膜成纤维细胞中的NF-κB途径上调TSLP，而地塞米松和干扰素（IFN）-γ可下调该途径。目前的研究结果表明，TSLP可能参与炎症性关节炎以及过敏性疾病 的病理生理过程。
