Cytokine Signalling Forum

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The JAK inhibitor CP-690,550 (tofacitinib) inhibits TNF-induced chemokine expression in fibroblast-like synoviocytes: autocrine role of type 1 interferon

Rosengren S, Corr M, Firestein GS, et al. - Annals of Rheumatic Diseases 2012; 71:440-47

This study investigated the effect of the novel Janus kinase (JAK) inhibitor CP-690,550 [tofacitinib] in fibroblast-like synoviocytes (FLSs) collected from patients with rheumatoid arthritis (RA). Human FLSs were cultured from the synovial tissue of patients with RA who were undergoing arthroplastic surgery, cultured and then serum-starved 48 hours prior to stimulation. Quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) or multiplex bead assay were used to measure messenger RNA and protein levels. Data showed that JAK and signal transducers and activators of the transcription (STAT) pathway in FLSs are indirectly activated by tumour necrosis factor (TNF) through autocrine expression of type I interferon (IFN), which ultimately results in increased production of T-cell cytokines. The study findings suggested that CP-690,550 [tofacitinib] is able to reduce chemokine synthesis by FLSs and so limits the recruitment of T-cells and other infiltrating leucocytes.