TLR2 Activation is Essential to Induce a Th1 Shift in Human Peripheral Blood Mononuclear Cells by Plant Stanols and Plant Sterols

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2009 Dec 2

PMID 19948716

Citations 19

Authors

Florence Brull

Ronald P Mensink

Karin van den Hurk

Adriaan Duijvestijn

Jogchum Plat

Affiliations

Soon will be listed here.

Abstract

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.

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