Background and aim: A number of lactic acid bacteria reside as normal microflora in human gut and some of them are reported to have lowering effect on serum cholesterol in human. In previous studies, we have demonstrated that heat killed Lactobacillus plantarum has hypocholesterolemic effect in mice. Lipoteichoic acid (LTA) is one of the main immunostimulatory components of gram-positive bacteria. Here, we investigated whether LTA from Lactobacillus plantarum (pLTA) could have anti-inflammatory effects in vitro and anti-atherosclerotic effects in high fat high cholesterol (HFHC) fed apoE-/- mice.
Methods and Results: pLTA pretreatment was done 12 hours before LPS stimulation. The secretion of TNF-α and IL-8 was inhibited by pLTA pretreatment in LPS stimulated THP-1 cells by 213% (p<0.038) and 40.3% (p<0.017), respectively. Pretreatment of THP-1 cells with pLTA inhibited degradation of IkB-α and activation of the NF-kB by LPS stimulation. These changes were accompanied by suppression of toll like receptor 2 (TLR2) and TLR4 expressions. In addition, in RAW264.7 cells stimulated with LPS, pretreatment of pLTA inhibited IkB-α degradation and secretion of TNF-α (41.3% decrease, p<0.019) as well as iNOS expression and nitric oxide production (32.8% decrease, p<0.034). Furthermore, ICAM-1, VCAM-1 and E-selectin expressions by TNF-α were also inhibited by pLTA pretreatment in a dose-dependent manner in human umbilical vein endothelial cells (HUVEC), resulting in suppression of THP-1 cell binding to HUVEC cells. In HFHC fed ApoE-/- mice treated with pLTA(intraperitoneal injection of 50 and 100g/kg weekly for 8 weeks) , atheroma volume and monocyte infiltration was reduced by 5% (p<0.07) and 12% (p<0.05), respectively, compared with reference group. Conclusion: Anti-inflammatory effect of pLTA might be beneficial in the treatment of atherosclerosis by inhibiting both inflammatory cytokine production from infiltrating immune cells and adhesion molecule expression on vascular endothelial cells.
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