Interleukin-18 protects splenectomized mice from lethal Streptococcus pneumoniae sepsis independent of interferon-gamma by inducing IgM production.

The mechanism of the susceptibility of splenectomized mice to Streptococcus pneumoniae infection and the therapeutic effect of interleukin (IL)-18 were investigated. We demonstrated that, although S. pneumoniae challenge induced IL-12 production, it did not induce either interferon (IFN)-gamma or IL-18 production in mice with or without a splenectomy.

Exploitation of interleukin-18 by gastric cancers for their growth and evasion of host immunity.

Interleukin-18 (IL-18) is a pleiotropic cytokine that enhances Th1 or Th2 immune response. We show a novel mechanism of gastric cancer cells that allows their immune escape utilizing IL-18. All 4 gastric cancer cell lines, but not colon lines, constitutively expressed IL-18 receptors and IL-18 dose-dependently enhanced their in vitro proliferation accompanied by nuclear factor kappaB activation.

Age-associated augmentation of the synthetic ligand- mediated function of mouse NK1.1 ag(+) T cells: their cytokine production and hepatotoxicity in vivo and in vitro.

We recently reported that the direct antitumor effectors in the liver induced by alpha-galactosylceramide (alpha-GalCer) are NK cells that are activated by the IFN-gamma produced from NK1.1 Ag(+) T cells (NKT cells) specifically stimulated with alpha-GalCer, whereas NKT cells cause hepatocyte injury through the Fas-Fas ligand pathway. In the present study, we investigated how mouse age affects the alpha-GalCer-induced effect using young (6-wk-old), middle-aged (30-wk-old), and old (75-wk-old) mice.

Growth-related signaling regulates activation of telomerase in regenerating hepatocytes.

Although there have been many reports on the relationship between activation of telomerase and carcinogenesis, the role of telomerase in normal cellular growth is still unclear. In this study, we analyzed the relationship between upregulation of telomerase activity and cell cycle progression during the liver regeneration process by using an in vivo mouse two-thirds partial hepatectomy (PH) model as well as by using in vitro hepatocyte culture systems. Furthermore, we also investigated the effects of growth factors on telomerase activity during liver regeneration and the influence of MAPK pathway inhibitors (MEK inhibitors PD98059 and U0126; p38 MAPK inhibitor SB203580) on the telomerase activity of regenerating hepatocytes in vitro.