Basic—Alimentary TractProinflammatory Role of Leukocyte-Derived Egr-1 in the Development of Murine Postoperative Ileus
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Animals
Adult male and female mice of 2–4 months of age weighing 25–30 g were used. Homozygous wild-type (Egr-1+/+) (WT) and homozygous mutant Egr-1 knockout (Egr-1−/−) (KO) mice were obtained by crossing heterozygous mice bearing a targeted mutation of the Egr-1 gene because female homozygous knockout mice are infertile. The breeding pairs were kindly provided by Dr David Pinsky of Columbia University (originally generated in the laboratory of Dr Jeffrey Milbrandt14, 15, 16, 17). The University of
Intestinal Manipulation Activates and Up-Regulates the Expression of Egr-1
Intestinal manipulation initiates a complex molecular and cellular inflammatory response within the intestinal muscularis that leads to intestinal ileus. Here, we show that manipulation induces a significant, rapid, 55-fold up-regulation in Egr-1 mRNA within 3 hours from extracts of the harvested jejunal muscularis using real-time RT-PCR (Figure 1A). This induction then subsided over a period of the first 12 hours but stayed significantly elevated for up to 24 hours (7-fold). We also measured
Discussion
Previously, much attention has concentrated on discovering the specific mediators that are involved in causing postoperative ileus.6 However, in this study we focused on elucidating transcriptional events that transduce these inflammatory mediators. The major finding of the current study is that the transcription factor Egr-1 present in leukocytes plays a major role in the proinflammatory molecular response within the surgically activated postoperative intestinal muscularis externa. The above
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Supported by National Institutes of Health grants R01-GM58241, R01-DK068610, and P50-GM53789.
Conflicts of interest: No conflicts of interest exist.