TLR2 activation is essential to induce a Th1 shift in human peripheral blood mononuclear cells by plant stanols and plant sterols.

F.T. Brüll, R.P. Mensink, K. Van den Hurk, A.M. Duijvestijn, J. Plat

Research output: Contribution to journalArticleAcademicpeer-review

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 IFN gamma 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), IFN gamma 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.

Original languageEnglish
Article number2951
Pages (from-to)2951-2958
Number of pages8
JournalJournal of Biological Chemistry
Volume285
Issue number5
DOIs
Publication statusPublished - 29 Jan 2010

Keywords

  • TOLL-LIKE-RECEPTORS
  • REGULATORY T-CELLS
  • IMMUNE-RESPONSE
  • BETA-SITOSTEROL
  • TH1/TH2 BALANCE
  • CYTOKINE
  • DISEASE
  • PHYTOSTEROLS
  • MICE
  • TARGET

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