Pathogenesis of Helicobacter pylori infection.
Much interest has been shown in the relationship between Helicobacter pylori infection and gastric carcinogenesis. It is becoming clearer that H. pylori strains carrying a functional cag pathogenicity island (cagPAI), which encodes the type IV secretion system (TFSS) and its effector CagA, play an important role in the development of gastric carcinoma. Furthermore, genetic polymorphism present in the cagA gene appears to influence the degree of an individual cagPAI-positive H. pylori to elicit gastric mucosal lesions, and this process is significantly affected by host genetic polymorphisms such as proinflammatory cytokine gene polymorphisms. Pathomechanism of gastric carcinogenesis associated with H. pylori includes bacteria-host interaction leading to morphologic alterations such as atrophic gastritis and gastrointestinal metaplasia mediated by COX-2 overexpression, cancer cell invasion, and neo-angiogenesis via TLR2/TLR9 system and transcription factors (e.g., NF-kappaB) activation. In addition, H. pylori infection triggers adhesion molecule expression and activity and produces an enhancement in oxidative stress interacting with gastric production of appetite hormone ghrelin and nonsteroidal anti-inflammatory drugs.
Hatakeyama
Masanori
M
Division of Molecular Oncology Institute for Genetic Medicine Hokkaido University, Sapporo, Japan. mhata@ig.hokudai.ac.jp
Brzozowski
Tomasz
T
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002648:Child; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005767:Gastrointestinal Diseases / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D016481:Helicobacter Infections / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D013274:Stomach Neoplasms / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; C080866:cagA protein, Helicobacter pylori