The intestinal tract is covered by a total of 300 square metres of IECs (intestinal epithelial cells) that covers the entire intestinal mucosa. For protection against luminal xenobiotics, pathogens and commensal microbes, these IECs are equipped with membrane-bound transporters as well as the ability to secrete specific protective proteins. In patients with active IBD (inflammatory bowel disease), the expression of these proteins, e.g. ABC (ATP-binding cassette) transporters such as ABCG2 (ABC transporter G2) and defensins, is decreased, thereby limiting the protection against various luminal threats. Correct ER (endoplasmic reticulum)-dependent protein folding is essential for the localization and function of secreted and membrane-bound proteins. Inflammatory triggers, such as cytokines and nitric oxide, can impede protein folding, which causes the accumulation of unfolded proteins inside the ER. As a result, the unfolded protein response is activated which can lead to a cellular process named ER stress. The protein folding impairment affects the function and localization of several proteins, including those involved in protection against xenobiotics. In the present review, we discuss the possible inflammatory pathways affecting protein folding and eventually leading to IEC malfunction in patients with active IBD.
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August 2011
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Conference Article|
July 20 2011
Impeded protein folding and function in active inflammatory bowel disease
J. Jasper Deuring;
J. Jasper Deuring
1
1Erasmus MC – University Medical Centre Rotterdam, Department of Gastroenterology and Hepatology, 's-Gravendijkwal 230, Room L-462, 3015 CE Rotterdam, The Netherlands
1To whom correspondence should be addressed (email j.deuring@erasmusmc.nl).
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Maikel P. Peppelenbosch;
Maikel P. Peppelenbosch
1Erasmus MC – University Medical Centre Rotterdam, Department of Gastroenterology and Hepatology, 's-Gravendijkwal 230, Room L-462, 3015 CE Rotterdam, The Netherlands
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Ernst J. Kuipers;
Ernst J. Kuipers
1Erasmus MC – University Medical Centre Rotterdam, Department of Gastroenterology and Hepatology, 's-Gravendijkwal 230, Room L-462, 3015 CE Rotterdam, The Netherlands
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C. Janneke van der Woude;
C. Janneke van der Woude
2
1Erasmus MC – University Medical Centre Rotterdam, Department of Gastroenterology and Hepatology, 's-Gravendijkwal 230, Room L-462, 3015 CE Rotterdam, The Netherlands
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Colin de Haar
Colin de Haar
2
1Erasmus MC – University Medical Centre Rotterdam, Department of Gastroenterology and Hepatology, 's-Gravendijkwal 230, Room L-462, 3015 CE Rotterdam, The Netherlands
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Publisher: Portland Press Ltd
Received:
March 28 2011
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem Soc Trans (2011) 39 (4): 1107–1111.
Article history
Received:
March 28 2011
Citation
J. Jasper Deuring, Maikel P. Peppelenbosch, Ernst J. Kuipers, C. Janneke van der Woude, Colin de Haar; Impeded protein folding and function in active inflammatory bowel disease. Biochem Soc Trans 1 August 2011; 39 (4): 1107–1111. doi: https://doi.org/10.1042/BST0391107
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