Functional capabilities of probiotic strains on attenuation of intestinal epithelial cell inflammatory response induced by TLR4 stimuli

Biofactors. 2019 Mar;45(2):223-235. doi: 10.1002/biof.1475. Epub 2018 Dec 11.

Abstract

Intestinal epithelial cells (IECs) respond to intruders and their cellular molecules by displaying inflammatory state that can be abrogated by probiotics. However, the molecular mechanisms underlying the beneficial activity of probiotic strains have yet to be elucidated. This study was conducted to investigate whether probiotic strains have immunoregulatory effects in IECs, and how they respond to bacterial lipopolysaccharide (LPS) in vitro. Caco2 cells were stimulated with LABs and followed by LPS. The expression of different cytokines that involved in toll-like receptor (TLR) signaling was analyzed. Caco2 cells that were exposed to LPS showed upregulated expression of IL-6, CXCL8, CCL2, and BPI that were counteracted by LAB strains through the modulation of TLR negative regulators (A20, Tollip, SIGIRR, and IRAKM), p38 MAPK and p65 NF-κB signaling. Lactobacillus plantarum, L. farciminis, and L. pentosus unveiled better activity as compared to other strains. Moreover, LAB strains were the potent inducers of immunoregulatory cytokines in coculture system. The expression of IL-10 and TGF-β were found to be higher as compared with LPS. Conversely, TNF-α at the protein level was dampened by LAB strains in both the apical and basolateral compartments. Collectively, our results demonstrated that the selected LAB strains exert profound immunoregulatory effects in response to LPS on IECs; however, further studies in vivo and in clinical settings are important to corroborate these effects. © 2018 BioFactors, 45(2):223-235, 2019.

Keywords: anti-inflammation; immunomodulation; inflammatory response; intestinal epithelial cells; lipopolysaccharide; probiotics.

MeSH terms

  • Blotting, Western
  • Caco-2 Cells
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells / drug effects
  • Epithelial Cells / immunology*
  • Humans
  • Intestines / cytology*
  • Lactobacillales / drug effects
  • Lactobacillales / metabolism
  • Lipopolysaccharides / pharmacology
  • Probiotics / therapeutic use*
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Lipopolysaccharides
  • Toll-Like Receptor 4