Protein kinase CK2 is a critical regulator of epithelial homeostasis in chronic intestinal inflammationShow others and affiliations
2013 (English)In: Mucosal Immunology, ISSN 1933-0219, E-ISSN 1935-3456, Vol. 6, no 1, p. 136-145Article in journal (Refereed) Published
Abstract [en]
The molecular mechanisms that restore intestinal epithelial homeostasis during colitis are incompletely understood. Here, we report that during intestinal inflammation, multiple inflammatory cytokines promote the activity of a master regulator of cell proliferation and apoptosis, serine/threonine kinase CK2. Enhanced mucosal CK2 protein expression and activity were observed in animal models of chronic colitis, particularly within intestinal epithelial cells (IECs). The in vitro treatment of intestinal epithelial cell lines with cytokines resulted in increased CK2 expression and nuclear translocation of its catalytic alpha subunit. Similarly, nuclear translocation of CK2alpha was a prominent feature observed in colonic crypts from individuals with ulcerative colitis and Crohn's disease. Further in vitro studies revealed that CK2 activity promotes epithelial restitution, and protects normal IECs from cytokine-induced apoptosis. These observations identify CK2 as a key regulator of homeostatic properties of the intestinal epithelium that serves to promote wound healing, in part through inhibition of apoptosis under conditions of inflammation.
Place, publisher, year, edition, pages
Nature Publishing Group, 2013. Vol. 6, no 1, p. 136-145
Keywords [en]
Animals, Apoptosis/genetics, Casein Kinase II/genetics/*metabolism, Caspases/metabolism, Cell Line, Cell Nucleus/metabolism, Cell Proliferation, Colitis/chemically induced/genetics/*immunology/*metabolism, Disease Models, Animal, Epithelial Cells/metabolism, Gene Expression Regulation, Homeostasis/*immunology, Humans, Intestinal Mucosa/*immunology/*metabolism, Mice, Protein Transport, Rats, Wound Healing, beta Catenin/metabolism
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-141657DOI: 10.1038/mi.2012.57ISI: 000312895500014PubMedID: 22763408Scopus ID: 2-s2.0-84870943584ISBN: 1935-3456 (Electronic) 1933-0219 (Linking) OAI: oai:DiVA.org:liu-141657DiVA, id: diva2:1149713
Note
Koch, S Capaldo, C T Hilgarth, R S Fournier, B Parkos, C A Nusrat, A eng R01 DK079392/DK/NIDDK NIH HHS/ R01 DK072564/DK/NIDDK NIH HHS/ R24 DK064399/DK/NIDDK NIH HHS/ R01 DK055679/DK/NIDDK NIH HHS/ R01 DK061379/DK/NIDDK NIH HHS/ DK059888/DK/NIDDK NIH HHS/ R01 DK059888/DK/NIDDK NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2012/07/06 06:00 Mucosal Immunol. 2013 Jan;6(1):136-45. doi: 10.1038/mi.2012.57. Epub 2012 Jul 4.
2017-10-162017-10-162018-01-13Bibliographically approved