TLR2 activation is essential to induce a Th1 shift in human peripheral blood mononuclear cells by plant stanols and plant sterols.
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.
Brüll
Florence
F
Department of Human Biology, Maastricht University and School for Nutrition, Maastricht, The Netherlands.
Mensink
Ronald P
RP
van den Hurk
Karin
K
Duijvestijn
Adriaan
A
Plat
Jogchum
J
D000818:Animals; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D000071518:Liver X Receptors; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D010840:Phytosterols / Q000378:metabolism*; D010944:Plants / Q000378:metabolism*; D012855:Sitosterols / Q000378:metabolism*; D018417:Th1 Cells / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D020298:U937 Cells
D020382:Interleukin-18; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D010840:Phytosterols; D012855:Sitosterols; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D018664:Interleukin-12; D007371:Interferon-gamma; C021255:stigmastanol