Stimulation of the cholinergic inflammatory pathway can attenuate 
collagen-induced arthritis (CIA) and inhibit synovitis by Janus kinase (JAK) 2 
and signal transducer and activator of transcription (STAT) 3 signaling. 
Suppressor of cytokine signaling (SOCS) protein can also regulate the 
inflammatory processes and activate JAK/STAT signal transduction, but its 
involvement in rheumatoid arthritis (RA) has not been demonstrated. This study 
investigated the effect of SOCS on cholinergic pathway regulation of synovitis 
in the fibroblast-like synoviocytes (FLSs) of RA and CIA mice. The effects of 
nicotine on SOCS1 and SOCS3 protein expression in FLSs were assayed by western 
blotting before and after transfection with a small interfering RNA 
oligonucleotide (SOCS3-siRNA or control-siRNA). Interleukin-6 was measured by 
enzyme-linked immunosorbent assay of SOCS3-siRNA and control-siRNA transfected 
FLS culture supernatants. Histopathological evaluation and immunohistochemical 
staining of SOCS3 were performed in joint tissue sections of control, CIA model, 
vagotomy, and nicotine-treated DBA/1 mice. Nicotine increased SOCS3 expression 
in the FLSs of RA. The inhibitory effect of nicotine on inflammatory factors was 
abolished by siRNA knockdown of SOCS3 protein expression. Nicotine increased the 
expression of SOCS3 protein in the synovium and reduced synovitis and bone 
erosion in CIA mice.