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Gastroenterology. 2004 Apr;126(4):1030-43.

Role of interferon-stimulated responsive element-like element in interleukin-8 promoter in Helicobacter pylori infection.

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1
Department of Medicine, Veterans Affairs Medicial Center and Baylor College of Medicine, Houston, TX 77030, USA. yyamaoka@bcm.tmc.edu

Abstract

BACKGROUND & AIMS:

Gastric mucosal interleukin (IL)-8 levels are related to the presence of both the cag pathogenicity island (PAI) and OipA. We investigated the regions of the IL-8 promoter and the upstream signaling involved in IL-8 gene transcription.

METHODS:

We cocultured parental Helicobacter pylori and isogenic oipA, hopZ, or cagE gene knockout mutants with gastric cancer cells. The regulatory sites in the IL-8 promoter were examined by luciferase reporter gene assay, electrophoretic mobility shift assays, and immunoblot analyses. Phosphorylated signal transducers and activators of transcription 1 (STAT1) levels in the antral gastric mucosa were measured by enzyme-linked immunosorbent assay.

RESULTS:

Maximal H. pylori -induced IL-8 gene transcription required the presence of the interferon-stimulated responsive element (ISRE)-like element, nuclear factor (NF)-kappa B and activator protein (AP)-1 binding sites. In vitro studies showed that OipA and the cag PAI were involved in inducing interferon regulatory factor (IRF)-1 to bind and activate the ISRE-like element and that the cag PAI, but not OipA, was involved in activating AP-1 and NF-kappa B. Both in vitro and in vivo studies showed that OipA, but not the cag PAI, was involved in STAT1 phosphorylation, as upstream signaling of IRF-1.

CONCLUSIONS:

OipA and the cag PAI are both necessary for full activation of the IL-8 promoter but act via different pathways that diverge upstream of IRF-1 where only OipA is involved in the STAT1-IRF1-ISRE pathway. The mucosal inflammatory response to H. pylori infection is complex and involves different pathways converging on the IL-8 promoter.

PMID:
15057743
[Indexed for MEDLINE]

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