INTRODUCTION: Interleukin (IL)-6-type cytokines exert their effects through 
activation of the Janus kinase/signal transducers and activators of 
transcription (JAK/STAT) signaling cascade. The JAK/STAT pathways play an 
important role in rheumatoid arthritis, since JAK inhibitors have exhibited 
dramatic effects on rheumatoid arthritis (RA) in clinical trials. In this study, 
we investigated the molecular effects of a small molecule JAK inhibitor, 
CP690,550 on the JAK/STAT signaling pathways and examined the role of JAK 
kinases in rheumatoid synovitis.
METHODS: Fibroblast-like synoviocytes (FLS) were isolated from RA patients and 
stimulated with recombinant oncostatin M (OSM). The cellular supernatants were 
analyzed using cytokine protein chips. IL-6 mRNA and protein expression were 
analyzed by real-time PCR method and ELISA, respectively. Protein 
phosphorylation of rheumatoid synoviocytes was assessed by Western blot using 
phospho-specific antibodies.
RESULTS: OSM was found to be a potent inducer of IL-6 in FLS. OSM stimulation 
elicited rapid phosphorylation of STATs suggesting activation of the JAK/STAT 
pathway in FLS. CP690,550 pretreatment completely abrogated the OSM-induced 
production of IL-6, as well as OSM-induced JAK/STAT, and activation of 
mitogen-activated kinases (MAPKs) in FLS.
CONCLUSIONS: These findings suggest that IL-6-type cytokines contribute to 
rheumatoid synovitis through activation of the JAK/STAT pathway in rheumatoid 
synoviocytes. Inhibition of these pro-inflammatory signaling pathways by 
CP690,550 could be important in the treatment of RA.