Intestinal epithelial cell signalling and chronic inflammation: From the proteome to specific molecular mechanisms.
Advancing knowledge regarding the cellular mechanisms of intestinal inflammation has led to a better understanding of the disease pathology in patients with inflammatory bowel disease (IBD) including Crohn's disease and ulcerative colitis. It has become clear from numerous studies that enteric bacteria are a critical component in the development and prevention/treatment of chronic intestinal inflammation. An emerging new paradigm suggests that changes in the homeostasis of bacteria- and host-derived signal transduction at the intestinal epithelial cell (IEC) level may lead to a break in barrier function and the development of adaptive immune disturbances. The functional loss of anti-inflammatory host-derived signals in the gut including the immunosuppressive cytokines Interleukin 10 (IL-10) and transforming growth factor (TGF)-beta are of high relevance to the pathogenesis of IBD. The development of analytical tools including two-dimensional (2D) high-resolution protein separation techniques and peptide mass fingerprinting via high-sensitivity mass-spectrometers (MS) allows the quantitative assessment of protein expression changes in disease-relevant cell types. By using these advanced methods, the characterization of the epithelial cell proteome from murine models of experimental colitis and human IBD patients identified novel disease-related mechanisms with respect to the regulation of the glucose-regulated endoplasmic reticulum stress response protein 78 (grp-78). In conclusion, the identification and functional analysis of differentially expressed proteins in purified intestinal target cell types will help to add important insights to the understanding of the molecular pathogenesis of these immune-mediated chronic intestinal disorders.
Werner
Tanja
T
Technical University of Munich, Experimental Nutritional Medicine, Else-Kroener-Fresenius-Center, Am Forum 5, 85350 Freising-Weihenstephan, Germany.
Haller
Dirk
D
D000818:Animals; D002908:Chronic Disease; D005759:Gastroenteritis / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000502:physiology*; D020543:Proteome / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D020543:Proteome