NF-kappaB activation and potentiation of proinflammatory responses by the Helicobacter pylori CagA protein.

Abstract:

:The Helicobacter pylori immunodominant protein, CagA, is associated with severe gastritis and carcinoma. Injection of CagA into gastric epithelial cells by type IV secretion leads to actin-cytoskeletal rearrangements and cell scattering. CagA has been reported to have no role in the induction of transcription factor NF-kappaB and IL-8, which are crucial determinants for chronic inflammation. Here, we provide several lines of evidence showing that CagA is able to induce IL-8 in a time- and strain-dependent manner. We also show that by exchanging specific cagA genes, high IL-8-inducing H. pylori strains could be converted into low inducing strains and vice versa. Our results suggest that IL-8 release induced by CagA occurs via a Ras-->Raf-->Mek-->Erk-->NF-kappaB signaling pathway in a Shp-2- and c-Met-independent manner. Thus, CagA is a multifunctional protein capable of effecting both actin remodeling and potentiation of chemokine release.

authors

Brandt S,Kwok T,Hartig R,König W,Backert S

doi

10.1073/pnas.0409873102

keywords:

subject

Has Abstract

pub_date

2005-06-28 00:00:00

pages

9300-5

issue

26

eissn

0027-8424

issn

1091-6490

pii

0409873102

journal_volume

102

pub_type

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