PROCEEDINGS |
The NF-kappaB/I kappaB protein complex is recognized as a major transcription regulator of inflammatory and immune responses. Many stimulants such as tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1, and lipopolysaccharides activate transcription by promoting dissociation of the complex and movement of NF-kappaB into the nucleus. Helicobacter pylori (H. pylori) infection, which causes chronic inflammation in gastric mucosa and often leads to gastirc malignancies, induces production of TNF-alpha, IL-1beta, IL-6, and IL-8 by normal gastric epithelium and gastric cancer cell lines. Expression of the IL-8 by surface mucous cells after H. pylori infection depends on activation of the NF-kappaB system via separation of I kappaB. However it has not been determined which isoform of I kappaB proteins functions in a complex with and as an inhibitor of NF-kappaB in gastric epithelia. To clarify which of the various known I kappaB proteins occur in gastric mucosa, we undertook immunohistochemical study in normal mouse stomach and other positive and negative control tissues using polyclonal antibodies specific for alpha, beta, gamma, and epsilon isoforms of I kappaB. The results showed strong immunoreactivity for the alpha isoform in parietal cells and for the beta isoform in surface mucous cells. Comparative staining showed the same distribution of these proteins in the Mongolian gerbil (Meriones unguiculatus), which is used as a model animal of H. pylori infection. The results suggest that the alpha and beta isoforms are dominant I kappaB proteins in gastric parietal and surface mucous cells, respectively, and point to a role for these transcription regulators in modulating pathologic responses in the stomach.