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Title
  • en Lactobacillus helveticus SBT2171 Induces A20 Expression via Toll-Like Receptor 2 Signaling and Inhibits the Lipopolysaccharide-Induced Activation of Nuclear Factor-kappa B and Mitogen-Activated Protein Kinases in Peritoneal Macrophages
Creator
    • en Kawano, Michio
    • en Miyoshi, Masaya
Accessrights open access
Rights
Subject
  • Other en lactic acid bacteria
  • Other en Lactobacillus helveticus SBT2171
  • Other en cytokine production
  • Other en antigen-presenting cell
  • Other en nuclear factor-kappa B
  • Other en mitogen-activated protein kinase
  • Other en A20
  • Other en toll-like receptor 2
  • NDC 490
Description
  • Abstract en Lactobacillus helveticus SBT2171 (LH2171) has been reported to ameliorate the development of autoimmune diseases, such as collagen-induced arthritis and experimental autoimmune encephalitis in mice and inhibit interleukin (IL)-6 production in antigen-presenting cells in vitro. Regulation of cytokine production by antigen-presenting cells might be critical for the anti-inflammatory function of LH2171 in autoimmune diseases. However, the mechanism and contributing components of LH2171-mediated inhibition of IL-6 production are unclear. Here, we examined the anti-inflammatory effects of LH2171 in lipopolysaccharide (LPS)-stimulated peritoneal macrophages, as a model of antigen-presenting cells, necessary for the pathogenesis of autoimmune diseases. LH2171 significantly reduced LPS-induced expression and secretion of IL-6 and IL-1 beta cytokines. It also inhibited activation of nuclear factor-kappa B and mitogen-activated protein kinases (NF-kappa B/MAPKs). Moreover, LH2171 induced gene expression of several negative regulators of NF-kB/MAPKs. Among these regulators, A20 was strongly up-regulated at the mRNA and protein levels upon LH2171 treatment. The cell wall fraction of LH2171 also demonstrated a similar increase in A20 gene expression and exerted an anti-inflammatory effect. These results suggest that the cell wall may be one of the anti-inflammatory components of LH2171. Since cell wall components of Gram-positive bacteria are recognized by toll-like receptor 2 (TLR2), we investigated whether the anti-inflammatory effect of LH2171 was mediated by TLR2 signaling. Specifically, LH2171-mediated IL-6 suppression and A20 upregulation in wild-type macrophages were reversed and significantly reduced in TLR2 knock-out macrophages. These results suggest that LH2171 induces A20 expression via TLR2 signaling, inhibiting the activation of NF-kB/MAPKs and cytokine production in antigen-presenting cells. This might contribute to the anti-inflammatory activity of LH2171 on autoimmune diseases.
Publisher en Frontiers Media
Date
    Issued2019-04-17
Language
  • eng
Resource Type journal article
Version Type VoR
Identifier HDL http://hdl.handle.net/2115/74438
Relation
  • isIdenticalTo DOI https://doi.org/10.3389/fimmu.2019.00845
  • PMID 31057558
Journal
    • PISSN 1664-3224
      • en Frontiers in immunology
      • Volume Number10 Page Start845
File
Oaidate 2023-07-26