IL-18 Upregulates the Production of Key Regulators of Osteoclastogenesis from Fibroblast-Like Synoviocytes in Rheumatoid Arthritis |
| |
Authors: | Wei Zhang Xiao-Liang Cong Yang-Hua Qin Zheng-Wen He Dong-Yi He Sheng-Ming Dai |
| |
Affiliation: | 1. Changzheng Hospital, Second Military Medical University, Shanghai, China 2. Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, People’s Republic of China 3. Department of Rheumatology, Shanghai Guanghua Hospital, 540 Xinhua Road, Shanghai, 200052, People’s Republic of China
|
| |
Abstract: | Recent data have demonstrated the importance of IL-18 in the induction and perpetuation of chronic inflammation in experimental arthritis. The aim of the present study was to elucidate whether IL-18 has any indirect effects on osteoclastogenesis by regulating the production of molecules from fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). Human FLS were isolated from RA synovial tissue and cultured in vitro for three to five passages. The expression of IL-18 receptor was determined by RT-PCR. The levels of soluble receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), macrophage colony-stimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in culture supernatants were determined by ELISA. Membrane-bound RANKL expression was analyzed by flow cytometry. Both α and β chains of IL-18 receptor were confirmed in cultured FLS. IL-18 upregulated membrane-bound RANKL expression and soluble RANKL production by FLS in both time- and dose-dependent manners. In addition, IL-18 enhanced production of M-CSF, GM-CSF, and OPG from cultured FLS in a dose-dependent manner. IL-18 also increased the ratio of RANKL/OPG, suggesting that the net effect of IL-18 on FLS favors for the induction of osteoclast formation and bone resorption. In conclusion, IL-18 upregulates the production of key regulators of osteoclastogenesis from FLS in RA. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|