Interleukin 1beta Induces Gastric Epithelial Cell Matrix Metalloproteinase Secretion and Activation During Helicobacter Pylori Infection

Overview

Journal Gut

Specialty Gastroenterology

Date 2003 Aug 13

PMID 12912854

Citations 12

Authors

M Gooz

M Shaker

P Gooz

A J Smolka

Affiliations

Soon will be listed here.

Abstract

Background: and aims: Matrix metalloproteinases (MMPs) are endopeptidases with roles in extracellular matrix remodelling, cell proliferation, and inflammatory processes. We showed previously that Helicobacter pylori infection of human gastric adenocarcinoma (AGS) cells increased epithelial secretion of epithelial MMP-1 and MMP-3 and bacterial secretion of MMP-3-like activity. In the present study, we sought to characterise the role of interleukin (IL)-1beta in H pylori induced secretion of epithelial MMPs.

Methods And Results: AGS cells were treated with H pylori and/or IL-1beta. Comparable IL-8 secretory responses (approximately 1700 ng/ml) measured by ELISA were induced by 2.0 ng/ml IL-1beta and by H pylori at a multiplicity of infection (MOI) of 50. The same IL-1beta and H pylori concentrations induced comparable increases in AGS cell caseinolytic activity at 60 kDa. MMP-3 monoclonal antibody immunoblots of AGS cell conditioned media detected immunoreactive bands at 71 kDa and 56 kDa. H pylori (MOI=50-100) induced dose dependent increases in both bands whereas IL-1beta (0.2-2 ng/ml) induced dose dependent increases only in the 71 kDa band, which was identified as a MMP-3/TIMP-3 (tissue inhibitor of metalloproteinases 3) heterodimer. AGS/H pylori conditioned media expressed 24 times more MMP-3 activity than AGS/IL-1beta conditioned media. There was a strong interaction between IL-1beta and H pylori on MMP-3 secretion.

Conclusions: We conclude that IL-1beta induces gastric epithelial cell MMP-3 secretion, contributing to epithelial tissue destruction during H pylori infection. However, other bacterial/host factors are needed to mediate the full gastric epithelial cell MMP-3 secretory response induced by H pylori infection.

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