IL-12 Regulates an Endothelial Cell-Lymphocyte Network: Effect on Metalloproteinase-9 Production
Open accessAbstract
IL-12 is key cytokine in innate immunity and participates in tumor rejection by stimulating an IFN-γ-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-γ (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.
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In APOE3Ch, IPA analysis indicated activation of anti-angiogenic IL-12 signaling and predicted inactivation of IL-6.
“In APOE3Ch , IPA analysis indicated activation of anti‐angiogenic IL‐12 signaling, 47 along with predicted inactivation of IL‐6, an upstream regulator associated with inflammation, vascular activation, and coagulation. 48”
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Bussolino, F., Di Renzo, M. F., Ziche, M., Bocchietto, E., Olivero, M., Naldini, L., Gaudino, G., Tamagnone, L., Coffer, A., & Comoglio, P. M. (1992) · The Journal of cell biology · doi:10.1083/jcb.119.3.629 · Cited by 1,337 · see citing works
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- Voest, E. E., B. M. Kenyon, M. S. O'Reilly, G. Truitt, R. J. D'Amato, and J. Folkman. 1995. Inhibition of angiogenesis in vivo by interleukin 12. J. Natl. Cancer Inst. 87:581.
- Piali, L., C. Weber, G. LaRosa, C. R. Mackay, T. A. Springer, I. Clark-Lewis, and B. Moser. 1998. The chemokine receptor CXCR3 mediates rapid and shear- resistant adhesion-induction of effector T lymphocytes by the chemokines IP10 and Mig. Eur. J. Immunol. 28:961.
- Pruijt, J. F. M., W. E. Fibbe, L. Laterveer, R. A. Pieters, I. J. D. Lindley, L. Paemen, S. Masure, R. Willemze, and G. Opdenakker. 1999. Prevention of interleukin-8-induced mobilization of hematopoietic progenitors cells in rhesus monkeys by inhibitory antibodies against the metalloproteinase gelatinase B (MMP-9). Proc. Natl. Acad. Sci. USA 96:10863.
- Lode, H. N., R. Xiang, S. R. Duncan, A. N. Theofilopoulos, S. D. Gillies, and R. A. Reisfeld. 1999. Tumor-targeted IL-2 amplifies T cell-mediated immune response induced by gene therapy with single-chain IL-12. Proc. Natl. Acad. Sci. USA 96:8591.
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IL-12 enhances the antitumor actions of trastuzumab via NK cell IFN-γ production
Jaime-Ramirez, A. C., Mundy-Bosse, B. L., Kondadasula, S., Jones, N. B., Roda, J. M., Mani, A., Parihar, R., Karpa, V., Papenfuss, T. L., LaPerle, K. M., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1000328 · Cited by 100 · see citing works
Pineda‐Lopez, L., Aguillon, D., Villar‐Vesga, J., Valderrama‐Carmona, P., Guerrero, A., Upreti, A., Arevalo‐Alquichire, S., Correa, L., Mendez‐Castellanos, K., Castaño, D., et al. (2026) · Alzheimer's & Dementia · doi:10.1002/alz.71148 · Cited by 4 · see citing works
- Authors
- Mitola, S., Strasly, M., Prato, M., Ghia, P., & Bussolino, F.
- Affiliations
- University of Turin (IT)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-10-01
- Volume
- 171
- Issue
- 7
- Pages
- 3725-3733
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1923312916
- Cited by
- 58
- References
- 1
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 2 · 2012: 3
- FWCI
- 1.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Keywords
- IL-12, endothelial cells, lymphocytes, MMP-9, TIMP-1, CXCL10, CXCL9, chemokines, lymphocyte transmigration, extracellular matrix, angiogenesis, CD4+ T cells, CD8+ T cells, tissue damage
- MeSH terms
- Basement Membrane, Cell Communication, Cell Migration Inhibition, Cell Movement, Cells, Cultured, Chemotaxis, Leukocyte, DNA-Binding Proteins, Endothelium, Vascular, Extracellular Matrix, Humans, Leukocytes, Mononuclear, Signal Transduction, CD4-Positive T-Lymphocytes, Trans-Activators, Lymphocyte Subsets, Interleukin-12, Coculture Techniques, Chemokines, CXC, Matrix Metalloproteinase 9, Intercellular Signaling Peptides and Proteins, STAT1 Transcription Factor, Chemokine CXCL10, Chemokine CXCL9, Matrix Metalloproteinase Inhibitors
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