The genus Lactobacillus is considered as predominant bacteria in the gastrointestinal tract of humans and animals and has been associated with beneficial effects on the host. Although it has been well known that Lactobacillus alleviates intestinal inflammation, the precise mechanisms by which bacterial components of Lactobacillus attenuate the inflammatory responses in the intestine have not been clearly understood. In this study, we investigated the inhibitory effect of a major bacterial component, lipoteichoic acid of L. plantarum on the production of interleukin (IL)-8 in a human intestinal epithelial cell line, Caco-2 cells. Staphylococcus aureus significantly induced mRNA expression of IL-8, but lipoprotein deficient S. aureus did not induce the expression of IL-8 in Caco-2 cells. Among microbial components tested in this study, Pam2CSK4, which is known to mimic Gram-positive bacterial lipoproteins, significantly induced IL-8 expression in a dose-dependent manner in Caco-2 cells. Although heat-inactivated L. plantarum slightly inhibited Pam2CSK4-induced IL-8 mRNA expression, L. plantarum LTA (Lp.LTA), but not its peptidoglycan, significantly inhibited Pam2CSK4-induced IL-8 expression. De-acylated or de-alanylated Lp.LTA failed to inhibit Pam2CSK4-induced IL-8 production, suggesting that lipid and D-alanine moieties are critical for the inhibitory effect of Lp.LTA on Pam2CSK4-induced IL-8 expression. Pam2CSK4-induced Toll-like receptor 2 (TLR2) activation was significantly reduced by Lp.LTA in CHO/CD14/TLR2 cells. Furthermore, Lp.LTA remarkably diminished Pam2CSK4-induced the phosphorylation of p38 kinase and JNK. In addition, IκBα was degraded in the presence of Pam2CSK4, but the degradation of IκBα was not observed in the presence of Lp.LTA. Collectively, these results suggest that Lp.LTA inhibits Pam2CSK4-induced IL-8 production through the decrease of phosphorylation of MAP kinases such as p38 kinase and JNK and the blocking of IκBα degradation via the decreased TLR2 activation in human intestinal epithelial cells.
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Inhibitory effect of Lactobacillus plantarum lipoteichoic acid on Pam2CSK4-induced IL-8 production in Caco-2 cells