SYNERGISTIC INDUCTION OF CX3CL1 BY THE COMBINATION OF TUMOR NECROSIS FACTOR ALPHA AND INTERFERON GAMMA VIA THE NF-.KAPPA.B SIGNALLING PATHWAY IN OSTEOBLASTS OF RHEUMATOID ARTHRITIS

概要

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CX3CL1 is involved in the recruitment of cells into tissues undergoing inflammatory responses. To determine the regulation of CX3CL1 during inflammatory bone diseases, such as rheumatoid arthritis (RA), human osteoblasts (OB), derived from patients with RA or osteoarthritis (OA), were incubated in the presence or absence of various inflammatory stimuli, then assessed for soluble CX3CL1 (sCX3CL1) levels and the expression of CX3CL1 mRNA transcripts using ELISA and quantitative real-time PCR, respectively. Although either tumor necrosis factor (TNF) -α or interferon (IFN) -γ induced no or little sCX3CL1 secretion by either RA or OA OB for 24 hours incubation, OB stimulated in the presence of both TNF-α and IFN-γ resulted in a synergistic expression pattern for both sCX3CL1 protein and mRNA transcripts in a dose- and time-dependent manner: this effect was more marked in RA OB. The synergistic secretion and expression of OB-derived CX3CL1 were markedly inhibited by specific inhibitors for nuclear factor kappa B. These findings suggest that osteoblasts are an important cellular source of CX3CL1 and may have an important role in inflammatory bone-joint diseases, as well as in osteoclastogenesis.