STOMACH

Interleukin 1ß induces gastric epithelial cell matrix metalloproteinase secretion and activation during Helicobacter pylori infection

M Gööz^1,2, M Shaker¹, P Gööz^1,2, A J Smolka¹

¹ Gastroenterology and Hepatology Division, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA
² Rheumatology and Immunology Division, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA

Correspondence to:
Correspondence to:
Dr A J Smolka, Department of Medicine CSB 921E, Medical University of South Carolina, 96 Jonathan Lucas St, Charleston, SC 29425, USA;
smolkaaj{at}musc.edu

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)-1ß in H pylori induced secretion of epithelial MMPs.

Methods and results: AGS cells were treated with H pylori and/or IL-1ß. Comparable IL-8 secretory responses (1700 ng/ml) measured by ELISA were induced by 2.0 ng/ml IL-1ß and by H pylori at a multiplicity of infection (MOI) of 50. The same IL-1ß 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-1ß (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-1ß conditioned media. There was a strong interaction between IL-1ß and H pylori on MMP-3 secretion.

Conclusions: We conclude that IL-1ß 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.

Keywords: interleukin 1ß; gastric inflammation; matrix metalloproteinase; Helicobacter pylori

Abbreviations: IL, interleukin; TNF-, tumour necrosis factor ; MOI, multiplicity of infection; MMPs, matrix metalloproteinases; TIMP, tissue inhibitor of metalloproteinases; vacA, vacuolating cytotoxin; cagA, cytotoxin associated protein; PBS, phosphate buffered saline; ELISA, enzyme linked immunosorbent assay; SDS-PAGE, sodium dodecyl sulphate-polyacrylamide gel electrophoresis

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