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Werner, T.* ; Hoermannsperger, G.* ; Schuemann, K.* ; Hölzlwimmer, G. ; Tsuji, S.* ; Haller, D.*

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)

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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.

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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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