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␥ production, with no change in the production of IL-4 and IL-10. ␣-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␥ 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.The human body responds to infectious challenges by a wide variety of cellular and humoral responses, in which numerous cells and factors play a role. During these responses, CD4 ϩ

Immunomodulatory properties of Beta-sitosterol in pig immune responses

“…In this disease, driving Th1 or Th2 responses correlates with the severity of the fungal infection and Th1-type dominance can reduce severity. Finally, Brull et al [32] demonstrated that sitosterol is able to shift immunity towards a Th1 dominant response in humans, at least ex vivo, and this effect is a plant sterol specific one and not a sterol effect in general. Moreover, they clearly demonstrated that TLR2 activation was essential to induce this Th1 shift in human PBMCs by plant stanols and plant sterols.…”

Plant sterols: Friend or foe in CNS disorders?

“…For instance, both nonmodified and modified phytosterols suppress an inflammatory transcriptional profile in macrophages [42,[182][183][184][185][186][187][188]. Furthermore, plant sterols and plant stanols skew T cells toward a Th1 phenotype independently of their effect of antigen-presenting cells (APCs) and leaving the activity of Th2 cells unaffected [180,189,190]. With respect to MS, sitosterol has been reported to decrease the secretion of the inflammatory mediators TNFa and IL-12 by PBMCs from MS patients at physiological relevant concentrations [181].…”

“…Numerous studies have reported immunomodulatory properties of phytosterols [38,42,114,[180][181][182][183]. For instance, both nonmodified and modified phytosterols suppress an inflammatory transcriptional profile in macrophages [42,[182][183][184][185][186][187][188].…”

Flax-seed oil and Lactobacillus plantarum supplementation modulate TLR and NF-κB gene expression in enterotoxigenic Escherichia coli challenged gnotobiotic pigs

“…by phytosterols. Brüll et al (2010) demonstrated TLR2 activa-tion in human peripheral blood mononuclear cells by plant stanols and plant sterols. On the other hand, the same authors did not confirm the activation of TLR4.…”