Protein kinase CK2 is a critical regulator of epithelial homeostasis in chronic intestinal inflammation

• Type of Material: Article
• Authors: Stefan Koch, Emory University; Christopher Todd Capaldo, Emory University; Roland S. Hilgarth, Emory University; Benedicte Fournier, Emory University; Charles Parkos, Emory University; Asma Nusrat, Emory University
• Language: English
• Date: 2012-07-04
• Publisher: Nature Publishing Group: Open Access Hybrid Model Option A
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Society for Mucosal Immunology
• Final Published Version (URL): http://www.nature.com/mi/journal/v6/n1/full/mi201257a.html
• Title of Journal or Parent Work: Mucosal Immunology
• ISSN: 1933-0219
• Volume: 6
• Issue: 1
• Start Page: 136
• End Page: 145
• Grant/Funding Information: This study was supported by grants from the National Institutes of Health (R01 DK072564, R01 DK061379, and R01 DK079392 to C.A.P.; R01 DK055679 and DK059888 to A.N.; morphology and tissue culture support from digestive diseases minicenter grant (DDRDC) R24 DK064399); and the Crohn's and Colitis Foundation of America (Research Fellowship Award to S.K. and C.T.C.).
• Research Categories: Health Sciences, Immunology

Abstract

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. In-vitro treatment of intestinal epithelial cell lines with cytokines resulted in increased CK2 expression and nuclear translocation of its catalytic α subunit. Similarly, nuclear translocation of CK2α was a prominent feature observed in colonic crypts from individuals with ulcerative colitis and Crohn's disease. Further invitro studies revealed that CK2 activity promotes epithelial restitution, and protects normal intestinal epithelial cells 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.