No abstract

The effect of Lactobacillus plantarum genomic DNA on lipopolysaccharide (LPS)-induced mitogen-activated protein kinase (MAPK) activation, nuclear factor-kappa B activation, and the expressions of tumor necrosis factor-alpha, interleukin-1 receptor-associated kinase M, and the pattern recognition receptor were examined. Pretreatment of p-gDNA inhibited the phosphorylation of MAPKs and nuclear factor-kappa B, and also inhibited LPS-induced TNF-α production in response to subsequent LPS stimulation. L. plantarum genomic DNA-mediated inhibition of signaling pathway and tumor necrosis factor-alpha was accompanied by the suppression of toll-like receptor (TLR) 2, TLR4, and TLR9 and the induction of interleukin-1 receptor-associated kinase M, a negative regulator of TLR. This study can extend our understanding of the biological function of probiotic genomic DNA as an anti-inflammatory agent.

Lipoteichoic acid (LTA) from Staphylococcus aureus (aLTA) and from Lactobacillus plantarum LTA (pLTA) are both recognized by Toll-like receptor 2 (TLR2), but cause different stimulatory effects on the innate immune and inflammatory responses, and their underlying cellular mechanisms are unknown. In this study, comparative proteome analysis was performed using two-dimensional gel electrophoresis and mass spectrometry on protein extracts from human monocyte THP-1 cells stimulated with either aLTA or pLTA. Differentially expressed proteins might be involved in innate immunity and inflammation. Cells treated with aLTA and with pLTA showed different protein expression profiles. Of 60 identified proteins, 10 were present only in treated cells (8 in aLTA-treated only, and 2 in pLTA-treated only), 1 protein (IMPDH2) was suppressed by pLTA, and 49 were up- or down-regulated more than three-fold by aLTA- or pLTA- stimulation. Several proteins involved in immunity or inflammation, antioxidation, or RNA processing were significantly changed in expression by aLTA- or pLTA-stimulation, including cyclophilin A, HLA-B27, D-dopachrome tautomerase, Mn- SOD, hnRNP-C, PSF and KSRP. These data demonstrated that aLTA and pLTA had different effects on the protein profile of THP-1 cells. Comparison of the proteome alterations will provide candidate biomarkers for further investigation of the immunomodulatory effects of aLTA and pLTA, and the involvement of aLTA in the pathogenesis of Staphylococcus aureus sepsis.

The lipoteichoic acid (LTA) of Staphylococcus aureus (aLTA) and Lactobacillus plantarum (pLTA) engage the same toll-like receptor 2 (TLR2) signaling pathway but exert different effects on innate immunity and inflammation. The mechanisms underlying these differential effects are not yet clear. Human oligonucleotide microarrays were used to investigate the transcriptome of human THP-1 monocytes upon exposure to aLTA or pLTA, and differential gene expression profiles were observed between the aLTA-and pLTA-treated cells. The expression level of 1,302 genes in aLTAtreated cells increased more than 2-fold; some of which have been implicated in immune or inflammatory responses, cell adhesion, cell signal transduction, transcription factors, anion transport, proteolysis, and oxidative processes. Particularly, a variety of genes that encode cytokines and chemokines, and TLR signaling-related molecules belonging to the tumor necrosis factor receptor-associated factor (TRAF), nuclear factor-kappa B, and signal transducer and activator of transcription families were remarkably up-regulated by aLTA stimulation. In contrast, pLTA treatment altered the expression of only 90 genes by more than 1.5-fold, and these genes were not correlated with innate immunity, inflammation or other related processes. The different effects mediated by aLTA and pLTA were further verified and compared by analysis of the expression of a selected group of genes, including TRAFs and some cytokines and chemokines, using real time-polymerase chain reaction and ELISA. These data suggest that aLTA and pLTA have different immunomodulatory potentials. Compared with pLTA, aLTA is a stronger stimulator and impacts the expression of many innate immunity-and/or inflammation-related genes.