Surface-Displayed IL-10 by Recombinant Lactobacillus plantarum Reduces Th1 Responses of RAW264.7 Cells Stimulated with Poly(I:C) or LPS

J Microbiol Biotechnol. 2016 Feb;26(2):421-31. doi: 10.4014/jmb.1509.09030.

Abstract

Recently, poly-γ-glutamic acid synthetase A (pgsA) has been applied to display exogenous proteins on the surface of Lactobacillus casei or Lactococcus lactis, which results in a surfacedisplayed component of bacteria. However, the ability of carrying genes encoded by plasmids and the expression efficiency of recombinant bacteria can be somewhat affected by the longer gene length of pgsA (1,143 bp); therefore, a truncated gene, pgsA, was generated based on the characteristics of pgsA by computational analysis. Using murine IL-10 as an exogenous gene, recombinant Lactobacillus plantarum was constructed and the capacity of the surface-displayed protein and functional differences between exogenous proteins expressed by these strains were evaluated. Surface expression of IL-10 on both recombinant bacteria with anchorins and the higher expression levels in L. plantarum-pgsA'-IL-10 were confirmed by western blot assay. Most importantly, up-regulation of IL-1β, IL-6, TNF-α, IFN-γ, and the nuclear transcription factor NF-κB p65 in RAW264.7 cells after stimulation with Poly(I:C) or LPS was exacerbated after co-culture with L. plantarum-pgsA. By contrast, IL-10 expressed by these recombinant strains could reduce these factors, and the expression of these factors was associated with recombinant strains that expressed anchorin (especially in L. plantarum-pgsA'-IL-10) and was significantly lower compared with the anchorin-free strains. These findings indicated that exogenous proteins could be successfully displayed on the surface of L. plantarum by pgsA or pgsA', and the expression of recombinant bacteria with pgsA' was superior compared with bacteria with pgsA.

Keywords: IL-10; Lactobacillus plantarum; RAW264.7; pgsA; surface display component.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / genetics*
  • Blotting, Western
  • Coculture Techniques
  • Interleukin-10 / genetics*
  • Interleukin-6 / metabolism
  • Lacticaseibacillus casei / genetics
  • Lactobacillus plantarum / drug effects
  • Lactobacillus plantarum / genetics*
  • Lipopolysaccharides / immunology
  • Membrane Proteins / genetics*
  • Mice
  • NF-kappa B / genetics
  • Poly I-C / immunology
  • RAW 264.7 Cells
  • Recombinant Proteins / immunology
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation

Substances

  • Bacterial Proteins
  • IL10 protein, mouse
  • Interleukin-6
  • Lipopolysaccharides
  • Membrane Proteins
  • NF-kappa B
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Poly I-C