Signaling mediated by the NF-κB sub-units NF-κB1, NF-κB2 and c-Rel differentially regulate Helicobacter felis-induced gastric carcinogenesis in C57BL/6 mice

摘要

The classical nuclear factor-kappaB (NF-魏B) signaling pathway has been shown to be important in a number of models of inflammation-associated cancer. In a mouse model of Helicobacter -induced gastric cancer, impairment of classical NF-魏B signaling in the gastric epithelium led to the development of increased preneoplastic pathology, however the role of specific NF-魏B proteins in Helicobacter- associated gastric cancer development remains poorly understood. To investigate this C57BL/6, Nfkb1 ~(鈭?鈭?/i>), Nfkb2 ~(鈭?鈭?/i>) and c-Rel ~(鈭?鈭?/i>) mice were infected with Helicobacter felis for 6 weeks or 12 months. Bacterial colonization, gastric atrophy and preneoplastic changes were assessed histologically and cytokine expression was assessed by qPCR. Nfkb1 ~(鈭?鈭?/i>) mice developed spontaneous gastric atrophy when maintained for 12 months in conventional animal house conditions. They also developed more pronounced gastric atrophy after short-term H. felis colonization with a similar extent of preneoplasia to wild-type (WT) mice after 12 months. c-Rel ~(鈭?鈭?/i>) mice developed a similar degree of gastric atrophy to WT mice; 3 of 6 of these animals also developed lymphoproliferative lesions after 12 months of infection. Nfkb2 ~(鈭?鈭?/i>) mice developed minimal gastric epithelial pathology even 12 months after H. felis infection. These findings demonstrate that NF-魏B1- and NF-魏B2-mediated signaling pathways differentially regulate the epithelial consequences of H. felis infection in the stomach, while c-Rel-mediated signaling also appears to modulate the risk of lymphomagenesis in gastric mucosa-associated lymphoid tissue.