IL-18 regulates IL-1β-dependent hepatic melanoma metastasis via vascular cell adhesion molecule-1

• DOI: 10.1073/pnas.97.2.734
• Publication Date: 2002-07-26T14:38:21Z
• Authors: Fernando Vidal-Va...; Giamila Fantuzzi; Lorea Mendoza; Angela M. Fuentes; Miren J. Anasagasti; Javier Martín; Teresa Carrascal; Patrick Walsh; Leonid L. Reznikov; Soo-Hyun Kim; Daniela Novick; Menachem Rubinstein; Charles A. Dinarello
• Keywords: Proinflammatory cytokine

Proinflammatory cytokines, including IL-1beta and tumor necrosis factor-alpha (TNF-alpha), promote cancer cell adhesion liver metastases by up-regulating the expression of vascular molecule-1 (VCAM-1) on hepatic sinusoidal endothelium (HSE). In this study, metastasis after intrasplenically injected mouse B16 melanoma (B16M) cells was reduced 84-95% in mice with null mutations for either or IL-1beta-converting enzyme (ICE, caspase-1) compared wild-type mice. On day 12, 47% were dead 19% ICE-deficient vitro, conditioned medium from B16M (B16M-CM) induced release TNF-alpha cultures primary murine HSE. The effect B16M-CM HSE resulted increased numbers adhering to HSE, which completely abrogated a specific inhibitor ICE, anti-IL-18 IL-18-binding protein. Exogenous IL-18 added also number cells; however, not affected IL-1 receptor blockade TNF neutralization but rather anti-VCAM-1. These results demonstrate role development vivo. soluble products stimulate sequentially TNF-alpha, IL-1beta, IL-18. cytokine increases VCAM-1 adherence cells.