IL-12 Regulates an Endothelial Cell-Lymphocyte Network: Effect on Metalloproteinase-9 Production

摘要: IL-12 is key cytokine in innate immunity and participates tumor rejection by stimulating an IFN-γ-mediated response characterized CD8+ mediated-cytotoxicity, inhibition of angiogenesis, vascular injury. We previously demonstrated that activated lymphocytes stimulated with induced angiostatic program cocultured endothelial cells. In this study, we have extended observation showing a reciprocal modulation cellular responses occurs. Actually, the presence cells enhanced inhibitory effect on metalloproteinase-9 expression PBMC as well their ability to transmigrate across extracellular matrix. triggered intracellular signaling, indicated STAT-1 activation, appeared mainly operative CD4 + challenged IL-12, but it was also initiated On other hand, reduced activity metalloproteinase-9, up-regulated tissue inhibitor metalloproteinase-1, pathway used neutralizing Abs show IFN-inducible protein 10 (CXCL10) monokine-induced IFN-γ (CXCL9) chemokines produced both are pivotal inducing these effects. Altogether results suggest existence IL-12-regulated circuit between endothelium resulting shift proteolytic homeostasis at site