|| Checking for direct PDF access through Ovid
Previous research has demonstrated that nicotine have protective role in rheumatoid arthritis(RA). However, the immunologic mechanisms of nicotine's effect have not been fully elucidated. Herein, the effects of nicotine on the differentiation of Th1, Th2, and Th17 cells were assessed.Peripheral blood mononuclear cells (PBMCs) and CD4+T cells were separated from patients with RA. PBMCs were stimulated with anti-CD3/anti-CD28 in the absence or presence of nicotine. CD4+T cells were cultured in the Th cell differentiation condition in the absence of nicotine or nicotine and alpha- bungarotoxin (αBgt) (the antagonist of nicotine) combined. Levels of T cell cytokines were detected with ELISA and flow cytometry. The expression of specific transcription factors (retinoic orphan re- ceptor c (RORc), T-box transcription factor (T-bet), and GATA Binding Protein 3 (GATA-3)) and signaling molecules (P-ERK1/2 and T-ERK1/2) were determined by Western blot. The results showed nicotine reduced IL-17A and increased IL-4 produced by stimulated PBMCs. During Th17 differentiation conditions, nicotine reduced the levels of IL-17A and RORc, induced the phosphorylation of ERK1/2. Meanwhile, nicotine increased the levels of IL-4 and GATA3 during Th2 differentiation. α-Bgt blocked the effects of nicotine on Th2 and Th17 differentiation. However, nicotine had no effect on the expression of IFN-γ and T-bet in CD4+T cells during Th1differentiation. These results demonstrate that nicotine suppresses Th17 differentiation, promotes Th2 differentiation and improves Th1/Th2 imbalance in RA patients, providing a new justification for its application in the treatment of rheumatoid arthritis.