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Interleukin-10 blocked endoplasmic reticulum stress in intestinal epithelial cells: impact on chronic inflammation.

Interleukin-10 blocked endoplasmic reticulum stress in intestinal epithelial cells: impact on chronic inflammation. Research Abstract Details 

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  • Interleukin-10 blocked endoplasmic reticulum stress in intestinal epithelial cells: impact on chronic inflammation. Abstract Text:

    anna shkodaAnna Shkoda,pedro a ruizPedro A Ruiz,hannelore danielHannelore Daniel,sandra c kimSandra C Kim,gerhard roglerGerhard Rogler,r balfour sartorR Balfour Sartor,dirk hallerDirk Haller,

    BACKGROUND & AIMS: The initiation of endoplasmic reticulum (ER)-mediated stress responses in intestinal epithelial cells (IEC) may contribute to the pathogenesis of chronic intestinal inflammation. The aim of the study was to use functional epithelial cell proteomics to characterize anti-inflammatory mechanisms of interleukin 10 (IL-10). METHODS: Primary IEC were isolated from Enterococcus faecalis-monoassociated IL-10-deficient (IL-10-/-) and wild-type mice to perform 2D-gel sodium-dodecyl-sulfate polyacrylamide gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. In addition, IEC from 6 patients with active Crohn's disease, ulcerative colitis, and sigmoid diverticulitis as well as noninflamed controls were purified. Molecular protective mechanisms of IL-10 were characterized in tumor necrosis factor (TNF)-stimulated IL-10 receptor (IL-10R) reconstituted epithelial cells. RESULTS: Primary IEC from IL-10-/- mice as well as inflammatory bowel disease patients revealed increased expression levels of the glucose-regulated ER stress protein (grp)-78 under conditions of chronic inflammation. Consistent with the observation that TNF induced ER stress responses through grp-78 redistribution from the ER lumen to the cytoplasmic IkappaB kinase complex, grp-78 knockdown completely abolished TNF-induced nuclear factor-kappaB RelA phosphorylation in epithelial cell cultures. Interestingly, IL-10 inhibited grp-78 protein and messenger RNA expression in IL-10R reconstituted IEC. Chromatin immunoprecipitation analysis and immunofluorescence microscopy revealed that IL-10-mediated p38 signaling inhibited TNF-induced recruitment of the ER-derived activating transcription factor (ATF)-6 to the grp-78 promoter likely through the blockade of ATF-6 nuclear translocation. CONCLUSIONS: Primary IEC from inflamed IL-10-/- mice and inflammatory bowel disease patients revealed activated ER stress responses in the intestinal epithelium. IL-10 inhibits inflammation-induced ER stress response mechanisms by modulating ATF-6 nuclear recruitment to the grp-78 gene promoter.

    Interleukin-10 blocked endoplasmic reticulum stress in intestinal epithelial cells: impact on chronic inflammation. Publishing Authors By Initials

    a shkodaA Shkoda,pa ruizPA Ruiz,h danielH Daniel,sc kimSC Kim,g roglerG Rogler,rb sartorRB Sartor,d hallerD Haller,

    For similar enzymes and coenzymes: enzymes: transferases: phosphotransferases: phosphotransferases (alcohol group acceptor): protein kinases: protein-serine-threonine kinases: mitogen-activated protein kinases: p38 mitogen-activated protein kinases research abstracts see: enzymes and coenzymes: enzymes: transferases: phosphotransferases: phosphotransferases (alcohol group acceptor): protein kinases: protein-serine-threonine kinases: mitogen-activated protein kinases: p38 mitogen-activated protein kinases research

    PUBMED ID PMID:

    MEDLINE DATE:

    Interleukin-10 blocked endoplasmic reticulum stress in intestinal epithelial cells: impact on chronic inflammation. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: Gastroenterology

    VOLUME: 132

    Page Numbers: 190-207

    Journal Abbreviation: Gastroenterology

    ISSN: 0016-5085

    DAY: 21

    MONTH: 10

    YEAR: 2006

    Interleukin-10 blocked endoplasmic reticulum stress in intestinal epithelial cells: impact on chronic inflammation. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 374630

    Interleukin-10 blocked endoplasmic reticulum stress in intestinal epithelial cells: impact on chronic inflammation. Keywords Mesh Terms:

    KEYWORDS: p38 Mitogen-Activated Protein Kinases

    MESH TERMS: metabolism

    Chemical & Substance for Abstract: Interleukin-10 blocked endoplasmic reticulum stress in intestinal epithelial cells: impact on chronic inflammation. Information

    Substance Name: p38 Mitogen-Activated Protein Kinases

    Registry Number: EC 2.7.1.37

    Grant and Affiliation Information for Interleukin-10 blocked endoplasmic reticulum stress in intestinal epithelial cells: impact on chronic inflammation.

    AFFILIATION: Else-Kroener-Fresenius Center for Experimental Nutritional Medicine, Technical University of Munich, 85350 Freising-Weihenstephan, Germany.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NIDDK

    GRANT: R01 DK 53347

    ACRONYM: DK

    MEDLINETA: Gastroenterology

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    ACCESSION NUMBER:

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