Induction effects of Faecalibacterium prausnitzii and its extracellular vesicles on toll-like receptor signaling pathway gene expression and cytokine level in human intestinal epithelial cells

Cytokine. 2019 Sep:121:154718. doi: 10.1016/j.cyto.2019.05.005. Epub 2019 May 29.

Abstract

A single layer of epithelial cells creates an interface between the host and microorganisms colonizing the gastrointestinal tract. In a healthy intestine, commensal bacteria and their metabolites can interact with epithelial cells as they are identified by Toll-like receptors (TLRs); This interaction results in homeostasis and immune responses. The present study aimed at evaluating Faecalibacterium prausnitzii- and extracellular vesicles (EVs)-induced expression of involved genes in TLRs signaling pathway and cytokines production in Caco-2 cell line. In this study, Caco-2 cell line was treated with F. prausitzii and its EVs. Using the protein levels of 12 cytokines were also evaluated by ELISA assay. F. prausnitzii induced upregulation in FOS, JUN, TNF-α, NFKB1, TLR3, IKBKB and CD86 genes. Furthermore, stimulation of Caco-2 cells with EVs derived from F. prausnitzii induced upregulation of CXCL8, CCL2, FOS, MAP2K4, TLR7, TLR3, IRF1, NFKBIA and TNF-α genes. Based on ELISA assay, Caco-2 cells treated with F. prausnitzii and its EVs showed a significant increase in TNF-α, IL-4, IL-8, and IL-10 expression and significant decreased in IL-1, IL-2, IL-6, IL-12, IL-17a, IFN-γ compared to the control group (P < 0.05). In conclusion, EVs derived from F. prausnitzii showed greater efficacy in decreasing the inflammatory cytokines and increasing the anti-inflammatory cytokines, compared to F. prausnitzii. Our findings can be used as a theoretical model for EVs application in the potential treatment of inflammation.

Keywords: Cytokine; Extracellular vesicles; Faecalibacterium prausnitzii; Gut microbiota; TLR signaling pathway.

MeSH terms

  • Caco-2 Cells
  • Chemokines / genetics
  • Chemokines / metabolism
  • Cluster Analysis
  • Cytokines / genetics*
  • Cytokines / metabolism
  • Down-Regulation / genetics
  • Enterocytes / metabolism*
  • Enterocytes / microbiology*
  • Extracellular Vesicles / metabolism*
  • Faecalibacterium prausnitzii / metabolism*
  • Gene Expression Regulation*
  • Humans
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction*
  • Toll-Like Receptors / metabolism*
  • Up-Regulation / genetics

Substances

  • Chemokines
  • Cytokines
  • RNA, Messenger
  • Toll-Like Receptors