Copper/zinc-loaded montmorillonite influences intestinal integrity, the expression of genes associated with inflammation, TLR4-MyD88 and TGF-β1 signaling pathways in weaned pigs after LPS challenge

Innate Immun. 2017 Nov;23(8):648-655. doi: 10.1177/1753425917733033. Epub 2017 Sep 29.

Abstract

This study was aimed at investigating whether dietary copper/zinc-loaded montmorillonite (Cu/Zn-Mt) could alleviate Escherichia coli LPS-induced intestinal injury through pro- and anti-inflammatory signaling pathways (TLRs, NLRs and TGF-β1) in weaned piglets. Eighteen 21-d-old pigs were randomly divided into three groups (control, LPS and LPS + Cu/Zn-Mt). After 21 d of feeding, pigs in the LPS group and LPS + Cu/Zn-Mt group received i.p. administration of LPS, whereas pigs in the control group received saline. At 4 h post-injection, jejunum samples were collected for analysis. The results indicated that, compared with the LPS group, supplemental Cu/Zn-Mt increased transepithelial electrical resistance, the expressions of anti-inflammatory cytokines (TGF-β1) in mRNA and protein levels, and decreased FD4 and the mRNA expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-8 and IL-1β). The pro-inflammatory signaling pathways results demonstrated that Cu/Zn-Mt supplementation decreased the mRNA levels of TLR4 and its downstream signals (MyD88, IRAK1, TRAF6) but had no effect on NOD1 and NOD2 signals. Cu/Zn-Mt supplementation did not affect NF-κB p65 mRNA abundance, but down-regulated its protein expression. The anti-inflammatory signaling pathways results showed supplemental Cu/Zn-Mt also increased TβRII, Smad4 and Smad7 mRNA expressions. These findings suggested dietary Cu/Zn-Mt attenuated LPS-induced intestinal injury by alleviating intestinal inflammation, influencing TLR4-MyD88 and TGF-β1 signaling pathways in weaned pig.

Keywords: Copper/zinc-loaded montmorillonite; Toll-like receptors; intestinal injury; nucleotide-binding oligomerization domain; transforming growth factor-β1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bentonite / chemistry
  • Bentonite / metabolism*
  • Copper / chemistry
  • Copper / metabolism*
  • Cytokines / metabolism
  • Inflammation / genetics
  • Inflammation Mediators / metabolism
  • Intestines / physiology*
  • Lipopolysaccharides / immunology
  • Myeloid Differentiation Factor 88 / metabolism*
  • Signal Transduction
  • Swine
  • Toll-Like Receptor 4 / metabolism*
  • Transforming Growth Factor beta1 / metabolism*
  • Weaning
  • Zinc / chemistry
  • Zinc / metabolism*

Substances

  • Cytokines
  • Inflammation Mediators
  • Lipopolysaccharides
  • Myeloid Differentiation Factor 88
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Transforming Growth Factor beta1
  • Bentonite
  • Copper
  • Zinc