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

Göõz, Monika; Shaker, Maria; Göőz, Pal; Smolka, Adam J.

doi:10.1136/gut.52.9.1250

Cited by 42 publications

(47 citation statements)

References 35 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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“…Although several previously reported transcriptional effects of IL-1␤ (9) were not observed to be significant up-regulation effects in this study, most likely due to the limited sensitivity of the microarray technique, a number of the observed upregulation effects during acute cholera are probably IL-1␤-induced effects. The up-regulated GDF15, MMP1, MMP3, and SERPINA3 genes are all known to be induced by IL-1␤ (3,7,16). The GDF15 gene codes for growth differentiation factor 15, a member of the transforming growth factor ␤ family that is expressed at high levels in epithelial cells, and, like SOCS3, seems to play a role in limiting the host response (36).…”

Section: Resultsmentioning

confidence: 99%

Broad Up-Regulation of Innate Defense Factors during Acute Cholera

et al. 2007

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We used a whole-genome microarray screening system (Affymetrix human GeneChips covering 47,000 different transcripts) to examine the gene expression in duodenal mucosa during acute cholera. Biopsies were taken from the duodenal mucosa of seven cholera patients 2 and 30 days after the onset of diarrhea, and the gene expression patterns in the acute-and convalescent-phase samples were compared pairwise. Of about 21,000 transcripts expressed in the intestinal epithelium, 29 were defined as transcripts that were up-regulated and 33 were defined as transcripts that were down-regulated during acute cholera. The majority of the up-regulated genes characterized were found to have an established or possible role in the innate defense against infections; these genes included the LPLUNC1, LF, VCC1, TCN1, CD55, SERPINA3, MMP1, MMP3, IL1B, LCN2, SOCS3, GDF15, SLPI, CXCL13, and MUC1 genes. The results of confirmative PCR correlated well with the microarray data. An immunohistochemical analysis revealed increased expression of lactoferrin in lamina propria cells and increased expression of CD55 in epithelial cells, whereas increased expression of the SERPINA3 protein (␣ 1 -antichymotrypsin) was detected in both lamina propria and epithelial cells during acute cholera. The expression pattern of CD55 and SERPINA3 in cholera toxin (CT)-stimulated Caco-2 cells was the same as the pattern found in the intestinal mucosa during acute cholera, indicating that the activation of the CD55 and SERPINA3 genes in intestinal epithelium was induced by CT. In conclusion, during acute cholera infection, innate defense mechanisms are switched on to an extent not described previously. Both direct effects of CT on the epithelial cells and changes in the lamina propria cells contribute to this up-regulation.

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“…Whereas several studies have confirmed the relationship between H. pylori infection and increased gastric mucosal MMP-1 (13)(14)(15), the relationship between gastric mucosal MMP-1 expression and the cag PAI and/or OipA virulence factors has not been examined. Enhanced MMP-1 expression has also been reported in H. pylori infection of AGS cells, a gastric epithelial cancer cell line (7,16), as well as in human gastric wall fibroblasts (14).…”

Section: Introductionmentioning

confidence: 90%

Balance between Polyoma Enhancing Activator 3 and Activator Protein 1 Regulates Helicobacter pylori–Stimulated Matrix Metalloproteinase 1 Expression

Lü

Sun

et al. 2006

Cancer Research

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Helicobacter pylori infection and elevated expression of tissue matrix metalloproteinase 1 (MMP-1) are both associated with gastric cancer. We investigated the regulation of MMP-1 expression during H. pylori infection. Real-time reverse transcription-PCR was used to examine mucosal MMP-1 mRNA levels in 55 patients with gastric cancers and 61 control patients. Increased MMP-1 mRNA levels in the gastric mucosa and epithelial cells were observed in H. pylori infections in which both the cag pathogenicity island (PAI) and outer inflammatory protein A (OipA) were expressed. The combined induction of c-fos, c-jun, and polyoma enhancing activator-3 (pea-3) by H. pylori caused maximal increase in MMP-1 expression. Activation of the MMP-1 promoter by H. pylori involved occupation of the activator protein 1 (AP-1) sites at À72 and À181 and, surprisingly, vacancy of the À88 PEA-3 site. Electrophoretic mobility shift, supershift, and chromatin immunoprecipitation assays showed increased binding of c-Fos and c-Jun to the À72 and À181 AP-1 sites during H. pylori infection. Importantly, during wild-type H. pylori infection, we detected increased PEA-3 binding to the À72AP-1 site and decreased PEA-3 binding to the À88 PEA-3 site. However, during infection with the cag PAI and oipA mutants, PEA-3 binding to the À88 site was detected. MMP-1 and pea-3 activities are increased in gastric cancers. Maximal activation of MMP-1 transcription requires the cag PAI and OipA, which regulate AP-1 and PEA-3 binding. Thus, cag PAI and OipA provide a possible link between bacterial virulence factors and important host factors related to disease pathogenesis.

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

Cited by 42 publications

References 35 publications

Gastric Transcription Profile of Helicobacter pylori Infection in the Rhesus Macaque

Gastric Transcription Profile of Helicobacter pylori Infection in the Rhesus Macaque

Broad Up-Regulation of Innate Defense Factors during Acute Cholera

Balance between Polyoma Enhancing Activator 3 and Activator Protein 1 Regulates Helicobacter pylori–Stimulated Matrix Metalloproteinase 1 Expression

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