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

S Brandt, T Kwok, R Hartig, W König… - Proceedings of the …, 2005 - National Acad Sciences
S Brandt, T Kwok, R Hartig, W König, S Backert
Proceedings of the National Academy of Sciences, 2005National Acad Sciences
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-κB 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 …
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-κB 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-κB 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.
National Acad Sciences