Lipoteichoic acid from Lactobacillus plantarum induces nitric oxide release in interferon-γ-primed macrophages (110.12)

Abstract Lactic acid bacteria are beneficial for human health by preventing microbial infections and reinforcing innate immunity in the gastrointestinal tract. Lipoteichoic acid (LTA) is known as a major immuno-stimulating agent of Gram-positive bacteria because of its potential to induce various inflammatory effector molecules. In the present study, we investigated whether highly-pure LTA from Lactobacillus plantarum induces nitric oxide (NO) in a murine macrophage-like cell line, RAW 264.7 cells. The LTA alone could not induce NO release even at 30 μg/ml but the combination of LTA and interferon (IFN)-γ enhanced NO release. The NO release was mainly mediated by inducible NO synthase (iNOS) since the NO release was inhibited by iNOS inhibitors, L-NIL or L-NAME, but not its stereoisomer, D-NAME. Upregulated mRNA and protein expression of iNOS was also observed in the presence of LTA and IFN-γ. In addition, LTA in the presence of IFN-γ induced IFN-γ expression and STAT-1 phosphorylation, both of which are the key pathways for inducing iNOS expression. Electrophoretic-mobility shift assay demonstrated that stimulation with the combination of LTA and IFN-γ remarkably increased the DNA-binding activities of NF-κB and AP-1 transcription factors which regulate the induction of iNOS gene expression. Collectively, these results indicate that LTA from L. plantarum alone has no inflammatory potential but it induces NO release under the inflamed conditions such as the presence of IFN-γ.