Institutional members access full text with Ovid®

Share this article on:

Epithelial Cell-Specific MyD88 Signaling Mediates Ischemia/Reperfusion-induced Intestinal Injury Independent of Microbial Status

Mühlbauer, Marcus MD, PhD*; Perez-Chanona, Ernesto MS*,†; Jobin, Christian PhD*,†

doi: 10.1097/01.MIB.0000435445.96933.37
Original Basic Science Articles

Abstract: The Toll-like receptor/MyD88 signaling pathway has been shown to mediate protective functions during intestinal exposure to various noxious events. The goal of this study was to define the role of bacteria and MyD88 signaling in intestinal response to damage using an ischemia–reperfusion (I/R)-induced injury model. We showed that conventionalized mice displayed a better outcome to I/R-induced injury than germ-free mice (3.8 ± 1.98 vs. 11.8 ± 1.83, P < 0.05). However, mice with intestinal epithelial cell (IEC)-specific deletion of Myd88 (Myd88 IEC−/−) were protected from I/R-induced injury compared with Myd88 f/f control mice. Myd88 IEC−/− mice also displayed a significantly reduced bacterial translocation (∼85%) into lymph nodes compared with Myd88 f/f mice. Expression of ccl2 and cxcl1 mRNA was significantly reduced (85% and 62%, respectively) in intestinal tissue of Myd88 IEC−/− mice compared with Myd88 f/f mice, which associated with a reduced number of myeloperoxidase-positive cells in intestinal tissues of I/R-exposed Myd88 IEC−/− mice. Immunohistochemistry analysis showed a reduced IgA deposition and complement staining in ischemic tissue of Myd88 IEC−/− mice compared with Myd88 f/f mice. These findings suggest that I/R-induced intestinal injury involves IEC-derived MyD88 signaling leading to increased IgA deposition/degradation, and complement activation in conjunction with an influx of neutrophils mediated by chemokine production.

Article first published online 17 October 2013Supplemental Digital Content is Available in the Text.

*Departments of Medicine, Microbiology and Immunology, and Pharmacology, University of North Carolina, Chapel Hill, North Carolina; and

Department of Medicine and Department of Infectious Diseases & Pathology, University of Florida, Gainesville, Florida.

Reprints: Christian Jobin, PhD, Department of Medicine, University of Florida, Gainesville, FL 32608 (e-mail:

Supported by National Institutes of Health grants R01DK047700 and R01DK073338 (C.J.) and Crohn's and Colitis Foundation of America (M.M.). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the article.

The authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Received August 13, 2013

Accepted September 11, 2013

© Crohn's & Colitis Foundation of America, Inc.
You currently do not have access to this article

To access this article:

Note: If your society membership provides full-access, you may need to login on your society website