PI3K/AKT/mTOR通路
mTORC1型
细胞因子
糖酵解
化学
肿瘤坏死因子α
乳酸脱氢酶A
细胞生物学
生物化学
生物
信号转导
酶
内分泌学
免疫学
作者
Katsunori Endo,Rina Matsui,Sugiyama Momona,Takuya Asami,Chihiro Inaba,Shuhei Kobayashi,Hidefumi Makabe,Sadao Tanaka
标识
DOI:10.1016/j.bcp.2020.113952
摘要
Procyanidins are polyphenols with antioxidant, anti-obesity, and anti-inflammatory properties. Procyanidin B2 (PCB2) gallate; specifically, PCB2 3,3″-di-O-gallate (PCB2DG), inhibits cytokine production in T cells. However, the molecular interactions and partners of PCB2DG underlying this suppression of cytokine production are unclear. The present study aimed to elucidate mechanisms underlying regulation of tumor necrosis factor (TNF)-α production by PCB2DG. We found that production of TNF-α and glycolytic activity in activated CD4+ T cells were suppressed by PCB2DG treatment. The inhibition of TNF-α production was found to be mediated by mammalian target of rapamycin (mTOR) and hypoxia inducible factor 1 (HIF-1) pathway, as PCB2DG suppressed the expression of HIF-1α, p-mTOR, and p-p70S6K (a downstream of the mTOR complex, mTORC1). Moreover, suppression of TNF-α production was mediated by regulation of the glycolytic enzyme lactate dehydrogenase at the posttranscriptional level. These results suggest that PCB2DG regulates TNF-α production by inhibiting glycolytic activity via the mTOR-HIF-1 pathway.
科研通智能强力驱动
Strongly Powered by AbleSci AI