title: 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.affiliation: Research Center, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, 07103-2400, USA. slomiabr@umdnj.edu
authors.forename: B L
authors.initials: BL
authors.lastname: Slomiany
authors.forename: J
authors.initials: J
authors.lastname: Piotrowski
authors.forename: A
authors.initials: A
authors.lastname: Slomiany
mesh_terms: D000818:Animals; D017209:Apoptosis; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D000072396:Endothelin-Converting Enzymes; D005753:Gastric Mucosa / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D005756:Gastritis / Q000139:chemically induced / Q000201:enzymology* / Q000276:immunology; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology*; D007249:Inflammation; D008666:Metalloendopeptidases / Q000378:metabolism; D011134:Polysaccharides / Q000633:toxicity*; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D011134:Polysaccharides; D011480:Protease Inhibitors; D014409:Tumor Necrosis Factor-alpha; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes