Effects of Helicobacter pylori CagA protein on the growth and survival of B lymphocytes, the origin of MALT lymphoma.
Helicobacter pylori (H. pylori) is a causative agent of gastrointestinal diseases such as atrophic gastritis and gastroduodenal ulcer. Infection of cagA-positive H. pylori is also associated with gastric carcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The cagA gene product CagA is directly injected into the bacteria-attached host cells via the bacterial type IV secretion system. The translocated CagA deregulates intracellular signaling pathways and thereby initiates pathogenesis. In this work, we examined the biological effects of CagA on B cells, from which MALT lymphoma arises. Ectopic expression of CagA in interleukin 3-dependent B cells inhibited cell proliferation by suppressing the JAK-STAT signaling. CagA was also capable of preventing hydroxyurea-induced B-cell apoptosis through inhibiting p53 accumulation. In contrast to the effects of CagA in gastric epithelial cells, the observed CagA activities in B cells were independent of its tyrosine phosphorylation. Our results indicate that CagA possesses both phosphorylation-dependent and -independent activities in mammalian cells and that biological impacts of CagA depend on cell-type context. As a result of B-cell growth inhibition, CagA may diminish anti-H. pylori immune responses. Furthermore, CagA may play a role in the development of MALT lymphoma by impairing p53-dependent apoptosis.
Umehara
Shintaro
S
Division of Molecular Oncology, Institute for Genetic Medicine and Graduate School of Science, Hokkaido University, Sapporo 060-0815, Japan.
Higashi
Hideaki
H
Ohnishi
Naomi
N
Asaka
Masahiro
M
Hatakeyama
Masanori
M
D001402:B-Lymphocytes / Q000166:cytology*; D001426:Bacterial Proteins / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology*; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000382:microbiology / Q000473:pathology*; D015398:Signal Transduction
D001426:Bacterial Proteins