Maintaining the Integrity of the Intestinal Epithelial Cell Barrier

Science's STKE  20 Mar 2007:
Vol. 2007, Issue 378, pp. tw93
DOI: 10.1126/stke.3782007tw93

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]