Helicobacter pylori upregulates matrilysin (MMP-7) in epithelial cells in vivo and in vitro in a Cag dependent manner

Bebb, James R.; Letley, Darren P.; Thomas, Russell J.; Avilés, Francisco de Asís Álvarez; Collins, Hilary M.; Watson, Susan A.; Hand, Neil M.; Zaitoun, Abed; Atherton, John C.

doi:10.1136/gut.52.10.1408

Cited by 79 publications

(76 citation statements)

References 45 publications

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“…Altered expression was found for several protease inhibitors, such as antithrombin III, serine protease inhibitor (Kazal type I), alpha-1-antitrypsin, and matrix metalloproteinase 3 (MMP-3) (all decreased) and MMP-15 (increased) (Tables 1 to 3). These results differ somewhat from recent studies using cultured gastric epithelial cells that demonstrated increased expression of proteases and protease inhibitors, such as MMP-1, -2, -3, -7, and -9 and ADAM (a disintegrin and metalloproteinase)-10 and -17 in gastric epithelial cells (9,10,24,38,48,63,99). Our results may emphasize differences between gene expression in cultured cells and an experimental animal model associated with H. pylori infection.…”

Section: Resultscontrasting

confidence: 56%

Gastric Transcription Profile of Helicobacter pylori Infection in the Rhesus Macaque

2004

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Infection with Helicobacter pylori is usually asymptomatic but sometimes progresses to peptic ulcer disease or gastric adenocarcinoma. The development of disease involves both host and bacterial factors. In order to better understand host factors in pathogenesis, we studied the gastric transcription profile of H. pylori infection in the rhesus macaque by using DNA microarrays. Significant changes were found in the expression of genes important for innate immunity, chemokines and cytokines, cell growth and differentiation, apoptosis, structural proteins, and signal transduction and transcription factors. This broad transcription profile demonstrated expected up-regulation of cell structural elements and the host inflammatory and immune response, as well as the novel finding of down-regulation of heat shock proteins. These results provide a unique view of acute H. pylori infection in a relevant animal model system and will direct future studies regarding the host response to H. pylori infection.

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Section: Resultscontrasting

confidence: 56%

Gastric Transcription Profile of Helicobacter pylori Infection in the Rhesus Macaque

2004

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“…In Hp-infected mucosa, epithelial cells appear to be one of the major sources of MMPs (19,20). Although Hp by itself can induce gastric epithelial cells to release MMPs (21,22), accumulating evidence indicates that cytokines produced by mucosal T cells and macrophages are also major stimuli for MMP production (16,23,24).…”

Section: Nfection By Helicobacter Pylori (Hp)mentioning

confidence: 99%

IL-21 Is Highly Produced in Helicobacter pylori-Infected Gastric Mucosa and Promotes Gelatinases Synthesis

Caruso

Fina

Peluso

et al. 2007

The Journal of Immunology

100

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Helicobacter pylori (Hp) infection is associated with gastric inflammation and ulceration. The pathways of tissue damage in Hp-infected subjects are complex, but evidence indicates that T cell-derived cytokines enhance the synthesis of matrix metalloproteinases (MMP) that contribute to mucosal ulceration and epithelial damage. In this study, we have examined the role of the T cell cytokine IL-21 in Hp-infected gastric mucosa and evaluated whether IL-21 regulates MMP production by gastric epithelial cells. We show that IL-21 is constitutively expressed in gastric mucosa and is more abundant in biopsy specimens and purified mucosal CD3+ T cells from Hp-infected patients compared with normal patients and disease controls. We also demonstrate that IL-21R is expressed by primary gastric epithelial cells, as well as by the gastric epithelial cell lines AGS and MKN28. Consistently, AGS cells respond to IL-21 by increasing production of MMP-2 and MMP-9, but not MMP-1, MMP-3, MMP-7, or tissue inhibitors of MMP. Analysis of signaling pathways leading to MMP production reveals that IL-21 enhances NF-κB but not MAPK activation, and inhibition of NF-κB activation reduces IL-21-induced MMP-2 and MMP-9 production. Finally, we show that treatment of Hp-infected gastric explants with anti-IL-21 reduces epithelial cell-derived MMP-2 and MMP-9 production. These data indicate that IL-21 is overexpressed in Hp-infected gastric mucosa where it could contribute to increased epithelial gelatinase production.

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“…So it could be deduced that MMP-7 might participate in the penetration of BM and ECM in gastric carcinomas instead of promoting cell proliferation. Recently, two studies demonstrated that MMP-7 upregulation was closely related with the H pylori cag pathogenicity island and this implied a certain role of MMP-7 in carcinogenesis of gastric carcinomas [35,36] . Invasion and metastasis of gastric carcinomas are a multistep process.…”

Section: A B C D E Fmentioning

confidence: 99%

Expression of heparanase gene, CD44v6, MMP-7 andnm23protein and their relationship with the invasion and metastasis of gastric carcinomas

Chen

Zhan²,

He³

et al. 2004

WJG

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AIM:To explore the expression of heparanase gene, CD44v6, MMP-7 and nm23 proteins in human gastric carcinoma as well as their relationship with the clinicopathological factors. METHODS:Reverse transcription polymerase chain reaction (RT-PCR) was used to measure the expressions of heparanase mRNA in 43 human gastric carcinomas and 10 adjacent normal gastric tissues. Streptavidin-peroxidase (S-P) two step method was used to measure the immunohistochemical expression of CD44v6, MMP-7 and nm23 protein in 43 human gastric carcinomas. RESULTS:The expression of heparanase gene was positive in 29 cases of gastric cancer with a positive rate of 67.4%, which was significantly higher than those in adjacent normal gastric tissues (P<0.05). The heparanase mRNA expression was significantly related to advanced stage of disease, serosal infiltration, lymph node metastasis and size of tumors (P<0.05), but not related to tumor location, gross and histological types of the cancer, peritoneal dissemination and liver metastasis (P>0.05). The positive rate of CD44v6, nm23 and MMP-7 proteins was 76.7%, 37.2% and 60.5%, respectively. The CD44v6 protein expression was significantly related to serosal infiltration, lymph node metastasis and TNM stage of disease (P<0.05). The nm23 protein expression was significantly related to the tumor gross appearance, lymph node and peritoneal metastasis (P<0.05). The MMP-7 protein expression was significantly related to serosal infiltration and TNM stage of disease (P<0.05). In an attempt to measure the association between these agents, we found that the expression of heparanase mRNA had significantly negative correlation with the expression of CD44v6 and MMP-7 protein (P<0.05), the expression of MMP-7 protein had significantly positive correlation with the expression of CD44v6 protein (r=0.568, P<0.05), the expression of MMP-7 protein had no correlation with the expression of nm23 protein (P>0.05), and the expression of nm23 protein had no correlation with the expression of CD44v6 protein (P>0.05). CONCLUSION:Despite their different mechanisms of action, heparanase, CD44v6 and nm23 may play important roles in the invasive infiltration and lymph node metastasis in gastric carcinomas. Instead of metastatic spreading, MMP-7 may be just related to the invasion of gastric carcinomas. However, co-detection of these factors may be important to predict metastatic spreading in such patients.

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Helicobacter pylori upregulates matrilysin (MMP-7) in epithelial cells in vivo and in vitro in a Cag dependent manner

Cited by 79 publications

References 45 publications

Gastric Transcription Profile of Helicobacter pylori Infection in the Rhesus Macaque

Gastric Transcription Profile of Helicobacter pylori Infection in the Rhesus Macaque

IL-21 Is Highly Produced in Helicobacter pylori-Infected Gastric Mucosa and Promotes Gelatinases Synthesis

Expression of heparanase gene, CD44v6, MMP-7 andnm23protein and their relationship with the invasion and metastasis of gastric carcinomas

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