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

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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

Cite this

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title = "TLR2 activation is essential to induce a Th1 shift in human peripheral blood mononuclear cells by plant stanols and plant sterols.",
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.",
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TLR2 activation is essential to induce a Th1 shift in human peripheral blood mononuclear cells by plant stanols and plant sterols. / Brüll, F.T.; Mensink, R.P.; Van den Hurk, K.; Duijvestijn, A.M.; Plat, J.

In: Journal of Biological Chemistry, Vol. 285, No. 5, 2951, 29.01.2010, p. 2951-2958.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - TLR2 activation is essential to induce a Th1 shift in human peripheral blood mononuclear cells by plant stanols and plant sterols.

AU - Brüll, F.T.

AU - Mensink, R.P.

AU - Van den Hurk, K.

AU - Duijvestijn, A.M.

AU - Plat, J.

PY - 2010/1/29

Y1 - 2010/1/29

N2 - 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.

AB - 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.

KW - TOLL-LIKE-RECEPTORS

KW - REGULATORY T-CELLS

KW - IMMUNE-RESPONSE

KW - BETA-SITOSTEROL

KW - TH1/TH2 BALANCE

KW - CYTOKINE

KW - DISEASE

KW - PHYTOSTEROLS

KW - MICE

KW - TARGET

U2 - 10.1074/jbc.M109.036343

DO - 10.1074/jbc.M109.036343

M3 - Article

VL - 285

SP - 2951

EP - 2958

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 5

M1 - 2951

ER -