期刊
GASTROENTEROLOGY
卷 126, 期 4, 页码 1030-1043出版社
W B SAUNDERS CO
DOI: 10.1053/j.gastro.2003.12.048
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资金
- NIAID NIH HHS [R01 AI40218, K08 AI01763] Funding Source: Medline
- NIDDK NIH HHS [DK56338] Funding Source: Medline
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)-kappaB 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-kappaB. 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.
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