Up-regulation of endothelin-converting enzyme-1 in gastric mucosal inflammatory responses to Helicobacter pylori lipopolysaccharide.

Abstract

Endothelin-1 (ET-1) is a vasoactive peptide produced from a biologically inactive big ET-1 by the action of endothelin-converting enzyme-1 (ECE-1). We investigated gastric mucosal expression of ECE-1 during a 10-day course of inflammatory responses associated with acute gastritis elicited by Helicobacter pylori lipopolysaccharide. The ECE-1 activity was associated with microsomal fraction and the level of its expression reflected the extent of mucosal inflammatory involvement. The histologic pattern of inflammation reached a maximum on the 4th day following the lipopolysaccharide and was accompanied by a 4.1-fold enhancement in the expression of ECE-1 activity and a significant elevation in ET-1 (3.1-fold), TNF-alpha (8.8-fold), and apoptosis (11.6-fold). A 41.5% decrease in the severity of mucosal inflammation by the 10th day following the lipopolysaccharide was reflected in a 62.3% reduction in the mucosal expression of ECE-1 and a decline in TNF-alpha, ET-1, and apoptosis. Thus, H. pylori infection causes up-regulation of gastric mucosal ECE-1 expression, which leads to the enhancement of ET-1 production, induction of TNF-alpha, and triggering the apoptotic events that exacerbate the inflammatory process.

• Authors: B L Slomiany, J Piotrowski, A Slomiany
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 267 Issue 3 Pg. 801-5 (Jan 27 2000) ISSN: 0006-291X [Print] United States
• PMID: 10673372 (Publication Type: Journal Article)
• Copyright: Copyright 2000 Academic Press.

Chemical References

• Polysaccharides
• Protease Inhibitors
• Tumor Necrosis Factor-alpha
• Aspartic Acid Endopeptidases
• Metalloendopeptidases
• Endothelin-Converting Enzymes

Topics

• Animals
• Apoptosis
• Aspartic Acid Endopeptidases (genetics, metabolism)
• Endothelin-Converting Enzymes
• Gastric Mucosa (enzymology, immunology, pathology)
• Gastritis (chemically induced, enzymology, immunology)
• Gene Expression Regulation, Enzymologic (immunology)
• Helicobacter pylori (immunology)
• Inflammation
• Metalloendopeptidases (metabolism)
• Polysaccharides (toxicity)
• Protease Inhibitors (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Time Factors
• Tumor Necrosis Factor-alpha (analysis)