Department of Human Biology, Maastricht University and School for Nutrition, Maastricht, The Netherlands.
J Biol Chem. 2010 Jan 29;285(5):2951-8. doi: 10.1074/jbc.M109.036343. Epub 2009 Nov 30.
Plant sterols may induce a Th1 shift in humans. However, whether plant stanols have similar effects as well as the underlying mechanism are unknown. We have now shown that (like sitosterol) sitostanol, both 4-desmethylsterols, induces a Th1 shift when added in vitro at physiological concentrations to human PBMCs. This conclusion was based on a higher IFNgamma production, with no change in the production of IL-4 and IL-10. alpha-Amyrin, a 4.4-dimethylsterol, had comparable effects. Because 4.4-dimethylsterols cannot activate transcription factor LXR, this finding indicates that LXR activation was not involved. Sitosterol and sitostanol did not alter the production of IL-12 and IL-18 in PBMCs as well as in monocyte-derived U937 cells, suggesting that plant sterols directly affect T-helper cells, without activating APCs. However, in PBMCs treated with a TLR2 blocker (T2.5), IFNgamma production was completely inhibited, whereas blocking TLR4 with HTA125 had no such effect. To confirm these findings, PBMCs from TLR2(-/-) mice were cultured in the presence of sitosterol and sitostanol. In these cells, no Th1 shift was observed. Our results, therefore, indicate that TLR2 activation is essential to induce a Th1 shift in human PBMCs by plant stanols and plant sterols.
植物固醇可能会诱导人体产生 Th1 偏移。然而，植物甾烷醇是否具有类似的作用以及潜在的机制尚不清楚。我们现在已经表明，（与甾醇类似）植物甾烷醇，这两种 4-去甲基固醇，在体外以生理浓度添加到人类 PBMC 中时会诱导 Th1 偏移。这一结论基于 IFNγ产量增加，而 IL-4 和 IL-10 产量没有变化。α-香树精，一种 4,4-二甲基固醇，具有类似的作用。因为 4,4-二甲基固醇不能激活转录因子 LXR，所以这一发现表明 LXR 激活不参与其中。植物固醇和植物甾烷醇不会改变 PBMC 中以及单核细胞衍生的 U937 细胞中 IL-12 和 IL-18 的产生，这表明植物固醇直接影响辅助性 T 细胞，而不激活 APC。然而，在 PBMC 中用 TLR2 阻断剂（T2.5）处理后，IFNγ的产生完全被抑制，而用 HTA125 阻断 TLR4 则没有这种效果。为了证实这些发现，用植物甾醇和植物甾烷醇培养 TLR2(-/-) 小鼠的 PBMC。在这些细胞中，没有观察到 Th1 偏移。因此，我们的结果表明，TLR2 的激活对于植物甾烷醇和植物固醇诱导人类 PBMC 产生 Th1 偏移是必不可少的。
