IL-18 Upregulates the Production of Key Regulators of Osteoclastogenesis from Fibroblast-Like Synoviocytes in Rheumatoid Arthritis

• Published in: Inflammation 2013-02, Vol.36 (1), p.103-109
• Main Authors: Zhang, Wei, Cong, Xiao-Liang, Qin, Yang-Hua, He, Zheng-Wen, He, Dong-Yi, Dai, Sheng-Ming
• Format: Article
• Language: English
• Subjects: Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - metabolism; Biomedical and Life Sciences; Biomedicine; Bone Resorption - metabolism; Cells, Cultured; Female; Gene Expression; Granulocyte-Macrophage Colony-Stimulating Factor - analysis; Humans; Immunology; Inflammation; Interleukin-18 - metabolism; Interleukin-18 Receptor alpha Subunit - biosynthesis; Interleukin-18 Receptor beta Subunit - biosynthesis; Internal Medicine; Macrophage Colony-Stimulating Factor - analysis; Middle Aged; Osteoclasts - drug effects; Osteoclasts - physiology; Osteogenesis; Osteoprotegerin - analysis; Pathology; Pharmacology/Toxicology; RANK Ligand - analysis; Rheumatology; Synovial Membrane - metabolism; Up-Regulation
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-012-9524-8

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.