Fig. 5: JAKinibs inhibit the expression of CXCR3-binding chemokines and TNFSF13B.

a RA-FLSs (n = 7) were pretreated with DMSO, baricitinib (250 nM) or tofacitinib (250 nM) for 1 h and then stimulated with TNF (10 ng/ml) for 6 h. Gene expression was determined by qPCR. Expression in the treated cells is presented relative to that in the unstimulated cells. Values are shown as the mean ± SEM. *p < 0.05, **p < 0.01; Wilcoxon matched-pairs test. b RA-FLSs were pretreated with DMSO, baricitinib (250 nM) or tofacitinib (250 nM) for 1 h and then stimulated with TNF (10 ng/ml) for 24 h. Western blots representative of at least four experiments with different RA-FLS cell lines are shown. c RA-FLSs were cultured in micromass organ cultures for 8 days. After serum starvation overnight, the FLSs were treated with DMSO (Unstimulated), TNF (10 ng/ml) + DMSO, TNF (10 ng/ml) + baricitinib (250 nM) or TNF (10 ng/ml) + tofacitinib (250 nM) for 24 h. Micromasses were fixed, sectioned and stained with hematoxylin and a specific antibody against TNFSF13B (brown staining). Images representative of four independent experiments performed with FLSs from four different RA patients are shown. d The schematic representation of the TNF-induced pathway in FLSs is shown (JAKinib = Janus Kinase inhibitor; IRG = interferon-regulated gene)