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Intestinal epithelial cell proteome from wild-type and TNF{Delta}ARE/WT mice: Effect of iron on the development of chronic ileitis.
J. Proteome Res. 8, 3252-3264 (2009)
Environmental factors substantially contribute to the development of chronic intestinal inflammation in the genetically susceptible host. Nutritional components like iron may act as pro-oxidative mediators affecting inflammatory processes and cell stress mechanisms. To better characterize effects of dietary iron on epithelial cell responses under the pathological conditions of chronic intestinal inflammation, we characterized the protein expression profile (proteome) in primary intestinal epithelial cells (IEC) from iron-adequate and low-iron fed wild-type (WT) and TNF Delta ARE/WT mice. We performed all possible comparisons between the 4 groups according to genotype or diet. Histological analysis of iron-adequate fed TNF Delta ARE/WT mice (similar to 0.54 mg of iron/day) revealed severe ileal inflammation with a histopathology score of 8.3 +/- 0.91 (score range from 0-12). Interestingly, low-iron fed mice (similar to 0.03 mg of iron/day) were almost completely protected from the development of inflammatory tissue destruction (histopathology score of 2.30 +/- 0.73). In total, we identified 74 target proteins with significantly altered steady state expression levels in primary IEC using 2D-gel electrophoresis (2D SDS-PAGE) and peptide mass fingerprinting via MALDI-TOF mass spectrometry (MS). Interestingly, the overlap between the comparison of iron-adequate fed WT and TNF Delta ARE/WT mice (inflamed conditions) and the comparison between the iron-adequate and iron-low fed TNF Delta ARE/WT mice (absence of inflammation) revealed 4 contrarily regulated proteins including aconitase 2, catalase, intelectin 1 and fumarylacetoacetate hydrolase (FAH). These proteins are associated with energy homeostasis, host defense, oxidative and endoplasmic reticulum (ER) stress responses. In conclusion, the iron-low diet affected the epithelial cell proteome and inhibited the development of chronic intestinal inflammation, suggesting a critical role for nutritional factors in the pathogenesis of IBD.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
IBD; Experimental ileitis; Iron; TNF Delta ARE/WT mice; Intestinal epithelial cells; Epithelial cell proteome; Aconitase 2; Catalase; Intelectin 1; FAH; inflammatory-bowel-disease; endoplasmic-reticulum stress; ulcerative-colitis; messenger-rna; gastrointestinal-tract; hereditary tyrosinemia; antioxidant defenses; responsive element; oxidative stress; crohns-disease
Language
english
Publication Year
2009
HGF-reported in Year
2009
ISSN (print) / ISBN
1535-3893
e-ISSN
1535-3907
Journal
Journal of Proteome Research
Quellenangaben
Volume: 8,
Issue: 7,
Pages: 3252-3264
Publisher
American Chemical Society (ACS)
Reviewing status
Peer reviewed
Institute(s)
Institute of Pathology (PATH)
POF-Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s)
Enabling and Novel Technologies
PSP Element(s)
G-500300-001
Scopus ID
67650355074
PubMed ID
19422269
Erfassungsdatum
2009-12-31