Helicobacter pylori strain-selective induction of matrix metalloproteinase-7 in vitro and within gastric mucosa |
| |
Authors: | Crawford Howard C Krishna Uma S Israel Dawn A Matrisian Lynn M Washington M Kay Peek Richard M |
| |
Institution: | Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, New York, USA. |
| |
Abstract: | BACKGROUND AND AIMS: Helicobacter pylori strains that possess the cag pathogenicity island (cag(+)) augment the risk for distal gastric cancer. Matrix metalloproteinase (MMP)-7, an epithelial cell-derived MMP that is induced by bacterial contact, is overexpressed within human gastric adenocarcinoma specimens and enhances tumor formation in rodents. We determined whether H. pylori alters MMP-7 expression and investigated the molecular pathways required for these events. METHODS: MMP-7 was detected in human gastric mucosa by immunohistochemistry and in H. pylori/AGS gastric epithelial cell coculture supernatants by Western analysis. AGS cells were cocultured with wild-type H. pylori, or isogenic cagA(-), cagE(-), or vacA(-) mutants, in the absence or presence of inhibitors of nuclear factor kappaB activation, p38, or extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase. RESULTS: H. pylori cag(+) strains increased MMP-7 expression in AGS cells 5-7-fold, whereas cag(-) isolates had no effect. Inactivation of cagE, but not cagA or vacA, completely attenuated induction of MMP-7, and inhibition of ERK 1/2 decreased MMP-7 production. In vivo, MMP-7 was expressed in gastric epithelial cells in specimens from 80% of cag(+)-colonized persons but in none of the cag(-) or uninfected subjects. CONCLUSIONS: H. pylori cag(+) strains enhance levels of MMP-7 within inflamed mucosa. In vitro, cag(+) isolates selectively induce MMP-7, and this is dependent on activation of ERK 1/2 by specific components within the cag island. Differential induction of MMP-7 by H. pylori cag(+) isolates may explain in part the augmentation in gastric cancer risk associated with these strains. |
| |
Keywords: | ERK extracellular signal-regulated kinase IL interleukin MAPK mitogen-activated protein kinase MEK mitogen-activated protein kinase kinase MMP matrix metalloproteinase NF-κB nuclear factor κB PCR polymerase chain reaction TBST Tris-buffered saline with 0 05% Tween 20 |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|