gms | German Medical Science

125. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

22. - 25.04.2008, Berlin

Critical Inflammatory Role of Egr-1 in Endotoxin Induced Ileus

Meeting Abstract

  • corresponding author J. Schmidt - Departement of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, USA
  • B. Stoffels - Departement of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, USA
  • J. Kalff - Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Deutschland
  • A. Hirner - Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Deutschland
  • A.J. Bauer - Departement of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, USA

Deutsche Gesellschaft für Chirurgie. 125. Kongress der Deutschen Gesellschaft für Chirurgie. Berlin, 22.-25.04.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. Doc08dgch9024

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgch2008/08dgch676.shtml

Veröffentlicht: 16. April 2008

© 2008 Schmidt et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Introduction: Early growth response gene-1 (Egr-1) has recently been linked to the transcriptional regulation of numerous inflammatory mediators. Endotoxin is known to activate the dense network of normally resident muscularis macrophages, which subsequently produce cytokines and chemokines that recruit monocytes into the muscularis externa resulting in sepsis induced ileus. Our objective was to mechanistically investigate the role of Egr-1 in endotoxin induced ileus.

Materials and methods: Wild-type and Egr-1 knockout mice were subjected to intraperitoneal LPS injection (5 mg/kg) to induce ileus. RT-PCR, Western blot and immunohistochemistry quantified and localized Egr-1. Intralumenal transit of non-absorbable FITC labeled dextran and calculated geometric centers measured gastrointestinal motility. Inflammatory mediator expressions were measured by RT-PCR, Griess reaction, ELISA and multiplex Luminex assay (N=4 each).

Results: LPS rapidly induced a 256±48.6 fold increase in Egr-1 mRNA and a 6.3±0.08 fold increase in protein at 90 min within the jejunal muscularis. Egr-1 was co-localized to extravasated monocytes 24 hours after endotoxin injection when ileus was functionally prominent. Egr-1-/- exhibited significantly less delay in gastrointestinal transit compared to wild-types (geometric center: WT=9.1±2.4, KO=7.8±2.1, WT-LPS=5.3±0.6 and KO-LPS=9.4±1.9). In Egr-1-/-, LPS induced significantly less IL-6 and MCP-1 mRNA and decreased release of nitric oxide, prostanoids, MCP-1, MIP-1α, MIG, KC, IP 10, IL-6, and GM-CSF with diminished recruitment of monocytes into the inflamed intestinal muscle wall compare to Egr-1+/+.

Conclusion: Our data demonstrates that Egr-1 plays a critical transcriptional, proinflammatory role in the initiation of the endotoxin induced inflammatory responses within the intestinal muscle layer which results in sepsis induced ileus.