Zhu Yongliang, Wang Caihua, Huang Jian, Ge Zhen, Dong Qi, Zhong Xian, Su Yanyan, Zheng Shu
Department of Gastroenterology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Cell Microbiol. 2007 Apr;9(4):952-61. doi: 10.1111/j.1462-5822.2006.00843.x. Epub 2006 Nov 28.
The Helicobacter pylori virulence factor, CagA, is causally linked to lymphoma of gastric mucosa-associated lymphoid tissue (MALT). However, it is unclear how CagA promotes the development of gastric MALT lymphoma. We investigated whether CagA modulates the activation of Erk1/2 and their downstream apoptosis regulators in B lymphocytes. Transfection of B1 lymphocytes with cagA transiently increased Erk1/2 phosphorylation, which was negatively regulated by MKP-1 and MKP-6. Activation of Erk1/2 led to phosphorylation of Bad at Ser-112, as confirmed with a chemical Erk1/2 inhibitor. However, CagA-induced Erk1/2 activation did not alter expression of either Bcl-2 or Bax. Importantly, cagA-transfected B1 cells were significantly protected against apoptosis induced by hydroxyurea. Our results reveal that CagA, to some extent like IL-3, can enhance lymphocytes' ability to evade apoptosis through phosphorylation of Bad. This may account, at least in part, for the ability of CagA to promote lymphomagenesis.
幽门螺杆菌毒力因子CagA与胃黏膜相关淋巴组织（MALT）淋巴瘤存在因果关联。然而，目前尚不清楚CagA如何促进胃MALT淋巴瘤的发展。我们研究了CagA是否调节B淋巴细胞中Erk1/2的激活及其下游凋亡调节因子。用cagA瞬时转染B1淋巴细胞可增加Erk1/2磷酸化，这受到MKP-1和MKP-6的负调控。如化学Erk1/2抑制剂所证实，Erk1/2的激活导致Bad在Ser-112位点磷酸化。然而，CagA诱导的Erk1/2激活并未改变Bcl-2或Bax的表达。重要的是，用cagA转染的B1细胞对羟基脲诱导的凋亡具有显著的保护作用。我们的结果表明，CagA在某种程度上类似于IL-3，可通过Bad磷酸化增强淋巴细胞逃避凋亡的能力。这可能至少部分解释了CagA促进淋巴瘤发生的能力。
