Procyanidin B2 gallates inhibit IFN-gamma and IL-17 production in T cells by suppressing T-bet and ROR gamma t expression

摘要

Procyanidins are widely found in plants and have anti-inflammatory activities. Procyanidin B2 (PCB2) inhibits production of proinflammatory cytokines in macrophages. However, there has been no study that has attempted to determine the effects of PCB2 gallates on T cell functions. In the present study, murine splenocytes were isolated and treated with PCB2 or PCB2 gallates in the presence of an anti-CD3 monoclonal antibody (mAb). PCB2 gallates, but not PCB2, inhibited proliferation and T cell activation of splenocytes after stimulation with the anti-CD3 mAb. In addition, PCB2 gallates, particularly 3,3"-di-O-gallate (3,3"-di-OG), significantly inhibited production of interferon (IFN)-y, interleukin (IL)-12p40, and IL-17 in splenocytes, but did not suppress IL-10 production. Intracellular staining revealed that the expression of IFN-gamma and IL-17 in both CD4(+) and CD8(+) T cells was obviously decreased by PCB2 3,3"-di-OG compared with PCB2, PCB2 3-OG, and PCB2 3"-OG. Treatment of isolated CD4+ and CD8+ T cells with procyanidins in the presence of the anti-CD3 mAb led to significant inhibition of IFNy production by PCB2 3,3"-di-OG in both cell types. Furthermore, PCB2 3,3"-di-OG suppressed the expression of transcription factors T-bet and ROR gamma t that regulate IFN-gamma and IL-17, respectively. In conclusion, we revealed a new mechanism through which PCB2 gallates inhibit IFN-gamma and IL-17 production in T cells by down-regulation of T-bet and ROR gamma t expression. Our results suggest that PCB2 gallates have a potential role in Thl/Thl 7-mediated diseases such as inflammatory and autoimmune diseases. (C) 2017 Elsevier B.V. All rights reserved.