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IL-12 regulates an endothelial cell-lymphocyte network: effect on metalloproteinase-9 production.

MITOLA, Stefania Maria Filomena;
2003-01-01
2003
Sogg. privati ital. no profit
LS3_7 Cell signalling and cellular interactions
JOURNAL OF IMMUNOLOGY
sì
2-s2.0-0142063394
WOS:000185548000051
Sì, ma tipo non specificato
Inglese
Internazionale
171
3725
3733
IL-12 is key cytokine in innate immunity and participates in tumor rejection by stimulating an IFN-gamma-mediated response characterized by CD8(+) mediated-cytotoxicity, inhibition of angiogenesis, and vascular injury. We previously demonstrated that activated lymphocytes stimulated with IL-12 induced an angiostatic program in cocultured vascular endothelial cells. In this study, we have extended this observation showing that a reciprocal modulation of cellular responses occurs. Actually, the presence of endothelial cells enhanced the inhibitory effect of IL-12 on metalloproteinase-9 expression in activated PBMC as well as their ability to transmigrate across an extracellular matrix. IL-12 triggered intracellular signaling, as indicated by STAT-1 activation, appeared to mainly operative in activated CD4 (+) cells challenged with IL-12, but it was also initiated in CD8(+) lymphocytes in the presence of endothelial cells. On the other hand, stimulated PBMC reduced the expression and the activity of metalloproteinase-9, up-regulated that of tissue inhibitor metalloproteinase-1, and stimulated the STAT-1 pathway in cocultured endothelial cells. We used neutralizing Abs to show that the IFN-inducible protein 10 (CXCL10) and monokine-induced by IFN-gamma (CXCL9) chemokines produced by both PBMC and endothelial cells are pivotal in inducing these effects. Altogether these results suggest the existence of an IL-12-regulated circuit between endothelium and lymphocytes resulting in a shift of proteolytic homeostasis at site of tissue injury..
Basement Membrane; CD4-Positive T-Lymphocytes; Cell Communication; Cell Migration Inhibition; Cell Movement; Cells; Cultured; Chemokine CXCL10; Chemokine CXCL9; Chemokines; CXC; Chemotaxis; Leukocyte; Coculture Techniques; DNA-Binding Proteins; Endothelium; Vascular; Extracellular Matrix; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-12; Leukocytes; Mononuclear; Lymphocyte Subsets; Matrix Metalloproteinase 9; STAT1 Transcription Factor; Signal Transduction; Trans-Activators.
MIUR (compresi PRIN FIRB,FISR)
5
info:eu-repo/semantics/article
262
Mitola, Stefania Maria Filomena; Strasly, M; Prato, M; Ghia, P; Bussolino, F.
1 Contributo su Rivista::1.1 Articolo in rivista
none
1.1 Articolo in rivista
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11379/21462
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