Thymic stromal lymphopoietin secretion of synovial fibroblasts is positively and negatively regulated by Toll-like receptors/nuclear factor-κB pathway and interferon-γ/dexamethasone
Thymic stromal lymphopoietin secretion of synovial fibroblasts is positively and negatively regulated by Toll-like receptors/nuclear factor-κB pathway and interferon-γ/dexamethasone
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DOI：
10.3109/s10165-007-0620-9
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发表时间：
2007-12
影响因子：
2.2
通讯作者：
Tetsuro Ozawa;Kensuke Koyama;Takashi Ando;Yuko Ohnuma;K. Hatsushika;Tetsuro Ohba;H. Sugiyama;Y. Hamada;H. Ogawa;K. Okumura;A. Nakao
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文献类型：
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作者：
Tetsuro Ozawa;Kensuke Koyama;Takashi Ando;Yuko Ohnuma;K. Hatsushika;Tetsuro Ohba;H. Sugiyama;Y. Hamada;H. Ogawa;K. Okumura;A. Nakao
胸腺基质淋巴生成素(TSLP)是一种由上皮细胞产生的白介素样细胞因子，可触发树突状细胞介导的Th2型变态反应性炎症反应。本研究探讨了Toll样受体(TLR)配体、脂多糖(LPS)和多聚IC对滑膜成纤维细胞TSLP产生的影响。酶联免疫吸附试验显示，LPS和PolyIC可上调类风湿性关节炎(RA)和骨关节炎(OA)患者滑膜成纤维细胞TSLP的生成。此外，我们还发现核因子-κB抑制剂IMD-0354、地塞米松和干扰素-γ可抑制内毒素和多聚IC诱导的RA和OA滑膜成纤维细胞中TSLP的产生。因此，脂多糖和多聚IC可通过NF-κB途径上调滑膜成纤维细胞中的TSLP，而地塞米松和干扰素-γ可下调其表达。目前的研究结果表明，TSLP可能参与了炎性关节炎和变态反应性疾病的病理生理过程。
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.