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IL-12 regulates an endothelial cell-lymphocyte network: effect on metalloproteinase-9 production.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2003 Oct 01; Vol. 171 (7), pp. 3725-33. - Publication Year :
- 2003
-
Abstract
- 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.
- Subjects :
- Basement Membrane enzymology
Basement Membrane immunology
CD4-Positive T-Lymphocytes immunology
Cell Migration Inhibition
Cell Movement immunology
Cells, Cultured
Chemokine CXCL10
Chemokine CXCL9
Chemokines, CXC biosynthesis
Chemokines, CXC physiology
Chemotaxis, Leukocyte immunology
Coculture Techniques
DNA-Binding Proteins biosynthesis
Endothelium, Vascular cytology
Extracellular Matrix enzymology
Extracellular Matrix immunology
Humans
Intercellular Signaling Peptides and Proteins biosynthesis
Intercellular Signaling Peptides and Proteins physiology
Interleukin-12 pharmacology
Leukocytes, Mononuclear cytology
Leukocytes, Mononuclear enzymology
Leukocytes, Mononuclear immunology
Lymphocyte Subsets cytology
Matrix Metalloproteinase Inhibitors
STAT1 Transcription Factor
Signal Transduction immunology
Trans-Activators biosynthesis
Cell Communication immunology
Endothelium, Vascular enzymology
Endothelium, Vascular immunology
Interleukin-12 physiology
Lymphocyte Subsets enzymology
Lymphocyte Subsets immunology
Matrix Metalloproteinase 9 biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 171
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 14500672
- Full Text :
- https://doi.org/10.4049/jimmunol.171.7.3725