Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. STKE, 20 March 2007
Vol. 2007, Issue 378, p. tw93
[DOI: 10.1126/stke.3782007tw93]


Epithelia Maintaining the Integrity of the Intestinal Epithelial Cell Barrier

John F. Foley

Science’s STKE, AAAS, Washington, DC 20005, USA

The cytokine IL-6 (interleukin-6), which has both pro- and antiinflammatory properties, helps to maintain epithelial barrier function in the intestine. Members of a family of structural proteins called keratins form the intermediate filaments in the cytoskeleton of epithelial cells and have been shown to protect cells from injury. A mutation in keratin-8 is found in some patients with inflammatory bowel disease, and mice deficient in keratin-8 develop colonic problems. Wang et al. uncovered a connection between IL-6 and keratins, particularly keratin-8, in studies performed using a human colonic epithelial cell line and IL-6 knockout mice. Treatment of Caco2-BBE cells with IL-6 increased both keratin-8 and keratin-18 at the level of mRNA and protein. The authors used confocal microscopy to show that IL-6 increased these keratins in the subapical region of Caco2-BBE epithelia. Analysis with phosphospecific antibodies showed that IL-6 treatment increased keratin-8 phosphorylation, which is important for the regulation of keratin organization and function. By monitoring the permeability of Caco2-BBE epithelia to fluorescein isothiocyanate-dextran, the authors showed that IL-6 treatment resulted in decreased permeability of the epithelial barrier. Experiments using RNA interference showed that this decreased permeability was mediated by keratin-8, although loss of keratin-8 had no effect on epithelial permeability in the absence of IL-6. IL-6-deficient mice treated with dextran sodium sulfate showed increased intestinal permeability in comparison with wild-type mice. Together, these data implicate keratin-8 in mediating the protective effects of IL-6 on the integrity of the intestinal epithelial layer.

L. Wang, S. Srinivasan, A. L. Theiss, D. Merlin, S. V. Sitaraman, Interleukin-6 induces keratin expression in intestinal epithelial cells. J. Biol. Chem. 282, 8219-8227 (2007). [PubMed]

Citation: J. F. Foley, Maintaining the Integrity of the Intestinal Epithelial Cell Barrier. Sci. STKE 2007, tw93 (2007).

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882