Accuri C6 Flow Cytometer System
Originally published online as doi:10.1189/jlb.0708396 on June 29, 2009

Published online before print June 29, 2009
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(Journal of Leukocyte Biology. 2009;86:971-980.)
© 2009 Society for Leukocyte Biology

TLR4-mediated Cox-2 expression increases intestinal ischemia/reperfusion-induced damage

Tiffany Moses*, Lynn Wagner{dagger} and Sherry D. Fleming*,1

* Division of Biology, Kansas State University, Manhattan, Kansas, USA; and
{dagger} U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland, USA

1. Correspondence: Division of Biology, 18 Ackert Hall, Kansas State University, Manhattan, KS 66506, USA. E-mail: sdflemin{at}ksu.edu

ABSTRACT

Mesenteric IR induces significant inflammation and immune-mediated mucosal damage. TLR4 is a critical receptor in the induction of the inflammatory response and plays a role in intestinal homeostasis. To determine the role of TLR4 in IR-induced epithelial damage, we performed IR studies using TLR4lps-def and TLR4lps-n mice and analyzed mucosal damage and inflammation. We found that the absence of TLR4 or TLR4-induced signaling attenuated local mucosal damage with significantly decreased cytokine and eicosanoid secretion including PGE2 production. Similar results were seen in MyD88–/– mice. Wild-type mice treated with NS-398 (a Cox-2 inhibitor) not only decreased PGE2 production but also attenuated tissue damage. In contrast, PGE2 was not sufficient to induce damage in the TLR4lps-def mice. Together, these data indicate that TLR4 stimulation of Cox-2 activation of PGE2 production is necessary but not sufficient for intestinal IR-induced damage and inflammation.

Key Words: eicosanoids • mice • innate autoimmunity