Inhibition of proinflammatory cytokine expression by NF-kappa B (p65) antisense oligonucleotide in Helicobacter pylori-infected mice

摘要

Background. Helicobacter pylori induces the expression of proinflammatory cytokines in vitro by activating nuclear factor-kappa B, a transcriptional regulator. However, it has not been clarified whether H. pylori-induced proinflammatory cytokines are also mediated through nuclear factor-kappa B in vivo. The aim of this study was to evaluate the role of nuclear factor-kappa B on the expressions of proinflammatory cytokines in H. pylori-infected mice. Materials and Methods. We evaluated nuclear factor-kappa B (p65) activation in the H. pylori-infected gastric mucosa of mice by immunofluorescent staining using antip65 polyclonal antibody, and the expressions of proinflammatory cytokines with inhibition of nuclear factor-kappa B pathway by using phosphorothioate antisense and sense oligonucleotide against the nuclear factor-kappa B (p65). Results. In the H. pylori-infected gastric mucosa of mice, immunofluorescent staining using antip65 polyclonal antibody showed nuclear factor-kappa B (p65) activation, which was particularly localized to epithelial cells. Tumor necrosis factor-alpha and interleukin-1 beta concentrations in gastric mucosa by enzyme-linked immunosorbent assay (ELISA) were elevated in the infected group versus the uninfected group. Pretreatment with nuclear factor-kappa B (p65) antisense oligonucleotide inhibited the activation of nuclear factor-kappa B and the expressions of tumor necrosis factor-alpha and interleukin-1 beta in H. pylori-infected gastric mucosa. Sense oligonucleotide did not influence on the expression of proinflammatory cytokines. Conclusions. H. pylori infection was found to activate the expressions of proinflammatory cytokines via nuclear factor-kappa B in vivo, and this may play an important role in the initiation of H. pylori-induced gastric inflammation.