Tomato lycopene extract prevents lipopolysaccharide-induced NF-kappaB signaling but worsens dextran sulfate sodium-induced colitis in NF-kappaBEGFP mice

PLoS One. 2009;4(2):e4562. doi: 10.1371/journal.pone.0004562. Epub 2009 Feb 23.

Abstract

Background: The impact of tomato lycopene extract (TLE) on intestinal inflammation is currently unknown. We investigated the effect of TLE on lipopolysaccharide (LPS)-induced innate signaling and experimental colitis.

Methodology/principal findings: Mice were fed a diet containing 0.5 and 2% TLE or isoflavone free control (AIN-76). The therapeutic efficacy of TLE diet was assessed using dextran sulfate sodium (DSS) exposed mice and IL-10(-/-);NF-kappaB(EGFP) mice, representing an acute and spontaneous chronic colitis model respectively. A mini-endoscope was used to determine the extent of macroscopic mucosal lesions. Murine splenocytes and intestinal epithelial cells were used to determine the in vitro impact of TLE on LPS-induced NF-kappaB signaling. In vitro, TLE blocked LPS-induced IkappaBalpha degradation, RelA translocation, NF-kappaB transcriptional activity and MIP-2 mRNA accumulation in IEC-18 cells. Moreover, LPS-induced IL-12p40 gene expression was dose-dependently inhibited in TLE-treated splenocytes. Interestingly, DSS-induced acute colitis worsened in TLE-fed NF-kappaB(EGFP) mice compared to control diet as measured by weight loss, colonoscopic analysis and histological scores. In contrast, TLE-fed IL-10(-/-);NF-kappaB(EGFP) mice displayed decreased colonic EGFP expression compared to control diet. IL-6, TNFalpha, and MCP-1 mRNA expression were increased in the colon of TLE-fed, DSS-exposed NF-kappaB(EGFP) mice compared to the control diet. Additionally, caspase-3 activation and TUNEL positive cells were enhanced in TLE diet-fed, DSS-exposed mice as compared to DSS control mice.

Conclusions/ significance: These results indicate that TLE prevents LPS-induced proinflammatory gene expression by blocking of NF-kappaB signaling, but aggravates DSS-induced colitis by enhancing epithelial cell apoptosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Carotenoids / pharmacology*
  • Colitis / chemically induced
  • Colitis / pathology*
  • Dextran Sulfate / pharmacology
  • Green Fluorescent Proteins
  • Inflammation / genetics
  • Inflammation / prevention & control
  • Intestinal Mucosa / pathology
  • Lipopolysaccharides / pharmacology
  • Lycopene
  • Mice
  • NF-kappa B / metabolism*
  • Plant Extracts
  • Signal Transduction / drug effects*
  • Solanum lycopersicum / chemistry

Substances

  • Lipopolysaccharides
  • NF-kappa B
  • Plant Extracts
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Carotenoids
  • Dextran Sulfate
  • Lycopene