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


RESULTS
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
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.
Joo
Young-Eun
YE
Department of Medicine and Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Karrasch
Thomas
T
Mühlbauer
Marcus
M
Allard
Brigitte
B
Narula
Acharan
A
Herfarth
Hans H
HH
Jobin
Christian
C
D000818:Animals; D002338:Carotenoids / Q000494:pharmacology*; D003092:Colitis / Q000139:chemically induced / Q000473:pathology*; D016264:Dextran Sulfate / Q000494:pharmacology; D049452:Green Fluorescent Proteins; D007249:Inflammation / Q000235:genetics / Q000517:prevention & control; D007413:Intestinal Mucosa / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D000077276:Lycopene; D018551:Solanum lycopersicum / Q000737:chemistry; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010936:Plant Extracts; D015398:Signal Transduction / Q000187:drug effects*
D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D002338:Carotenoids; D016264:Dextran Sulfate; D000077276:Lycopene