Lipoteichoic Acid Isolated from Lactobacillus plantarum Inhibits Lipopolysaccharide-Induced TNF-α Production in THP-1 Cells and Endotoxin Shock in Mice

Abstract

In this study, the effect of Lactobacillus plantarum lipoteichoic acid (pLTA) on LPS-induced MAPK activation, NF-κB activation, and the expression of TNF-α and IL-1R-associated kinase M (IRAK-M) was examined. The expression of the pattern recognition receptor and the survival rate of mice were also examined. pLTA pretreatment inhibited the phosphorylation of ERK, JNK, and p38 kinase. It also inhibited the degradation of IκBα and IκBβ, as well as the activation of the LPS-induced TNF-α factor in response to subsequent LPS stimulation. These changes were accompanied by the suppression of the LPS-induced expression of TLR4, NOD1, and NOD2, and the induction of IRAK-M, with a concurrent reduction of TNF-α secretion. Furthermore, the overexpression of pattern recognition receptors such as TLR4, NOD1, and NOD2 and the degradation of IRAK-M by transient transfection were found to reinstate the production of TNF-α after LPS restimulation. In addition, the i.p. injection of pLTA suppressed fatality, and decreased the level of TNF-α in the blood, in LPS-induced endotoxin shock mice. In conclusion, these data extend our understanding of the pLTA tolerance mechanism, which is related to the inhibition of LPS-induced endotoxin shock, and suggest that pLTA may have promise as a new therapeutic agent for LPS-induced septic shock.

Lactobacillus plantarum Lipoteichoic Acid Alleviates TNF-α-Induced Inflammation in the HT-29 Intestinal Epithelial Cell Line

“…The immunostimulatory activity of aLTA was remarkably diminished by removal of the fatty acid acyl group of LTA (Ohshima et al, 1988). We also demonstrated that the acyl group of pLTA was responsible for inhibiting LPS-induced TNF-a production, not the D-alanine substituent in the phosphoglycerol moiety of pLTA (Kim et al, 2008a). Based on the glycolipid analysis conducted in a previous study, the glycolipid moiety of pLTA contains unsaturated fatty acids and a third acyl chain on the conserved trihexosyldiacyl ceramide structure.…”

“…In a previous study, we have shown that pLTA inhibited LPS-or aLTA-induced TNF-α production in THP-1 cells (Kim et al, 2008a;2008b). In addition, pLTA has low immune activation effects while LPS and aLTA induce high levels of TNF-α production.…”

“…These LTAs may induce serious immune responses related to arthritis, nephritis, uveitis, encephalo-myelitis, meningeal inflammation, periodontal lesions, septic shock, and multiorgan failure. Although a previous study (Kim et al, 2008a) used pLTA for an in vivo septic shock mouse model, the application of LTAs to a human disease model is needed to learn more about their safety.…”

“…LTA inhibited rhTNF-α-induced IL-8 production Previously, we have shown that pLTA inhibited LPS-and aLTAinduced TNF-α production in THP-1 cells (Kim et al, 2008a;2008b). In this study, we examined the inhibitory effect of pLTA against rhTNF-α in HT-29 cells.…”

“…In addition, pLTA effectively inhibits aLTA-or LPS-triggered TNF-α secretion and suppresses the septic shock caused by aLTA or LPS stimulation (Kim et al, 2008a;2008b). The distinct immunological activities of aLTA and pLTA might contribute to the different physiological effects of S. aureus and L. plantarum on the human innate immune response.…”