IL-32 promotes angiogenesis
| Autor: | Yvonne Baumer, Carlyne D. Cool, Laszlo Farkas, Claudia A. Nold-Petry, Brent E. Palmer, Tania Azam, Ina Rudloff, Marcel F. Nold, Paolo Botti, Charles A. Dinarello, Hannah Dinkel, Leo A. B. Joosten, Jarod A. Zepp, Daniela Marasco, William A. Boisvert, Laima Taraseviciene-Stewart, Norbert F. Voelkel, Bas Heinhuis, Steven X. Cho, Menotti Ruvo |
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| Přispěvatelé: | C. A., Nold Petry, I., Rudloff, Y., Baumer, M., Ruvo, Marasco, Daniela, P., Botti, L., Farka, S. X., Cho, J. A., Zepp, T., Azam, H., Dinkel, B. E., Palmer, W. A., Boisvert, C. D., Cool, L., Taraseviciene Stewart, B., Heinhui, L. A. B., Joosten, C. A., Dinarello, N. F., Voelkel, M. F., Nold |
| Rok vydání: | 2014 |
| Předmět: |
Vascular Endothelial Growth Factor A
medicine.medical_specialty genetic structures Angiogenesis medicine.medical_treatment Hypertension Pulmonary Immunology lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] Apoptosis Biology Article Transforming Growth Factor beta1 chemistry.chemical_compound Interferon-gamma Mice Internal medicine medicine Human Umbilical Vein Endothelial Cells Immunology and Allergy Animals Humans Familial Primary Pulmonary Hypertension Cells Cultured Matrigel Integrin alphaVbeta3 Neovascularization Pathologic Interleukins Interleukin-8 Activins Endostatins Endothelial stem cell Vascular endothelial growth factor Vascular endothelial growth factor A Cytokine Endocrinology Receptors Vascular Endothelial Growth Factor chemistry Matrix Metalloproteinase 9 Protein chemical synthesis ELISA angiogenesis Cancer research Nitrogen Oxides Endostatin Glioblastoma |
| Zdroj: | Journal of Immunology, 192, 2, pp. 589-602 The Journal of immunology (1950) 192 (2014): 589–602. doi:10.4049/jimmunol.1202802 info:cnr-pdr/source/autori:Nold-Petry C.A.; Rudloff I.; Baumer Y.; Ruvo M.; Marasco D.; Botti P.; Farkas L.; Cho S.X.; Zepp J.A.; Azam T.; Dinkel H.; Palmer B.E.; Boisvert W.A.; Cool C.D.; Taraseviciene-Stewart L.; Heinhuis B.; Joosten L.A.B.; Dinarello C.A.; Voelkel N.F.; Nold M.F./titolo:IL-32 promotes angiogenesis/doi:10.4049%2Fjimmunol.1202802/rivista:The Journal of immunology (1950)/anno:2014/pagina_da:589/pagina_a:602/intervallo_pagine:589–602/volume:192 Journal of Immunology, 192, 589-602 |
| ISSN: | 0022-1767 |
| DOI: | 10.4049/jimmunol.1202802 |
| Popis: | Item does not contain fulltext IL-32 is a multifaceted cytokine with a role in infections, autoimmune diseases, and cancer, and it exerts diverse functions, including aggravation of inflammation and inhibition of virus propagation. We previously identified IL-32 as a critical regulator of endothelial cell (EC) functions, and we now reveal that IL-32 also possesses angiogenic properties. The hyperproliferative ECs of human pulmonary arterial hypertension and glioblastoma multiforme exhibited a markedly increased abundance of IL-32, and, significantly, the cytokine colocalized with integrin alphaVbeta3. Vascular endothelial growth factor (VEGF) receptor blockade, which resulted in EC hyperproliferation, increased IL-32 three-fold. Small interfering RNA-mediated silencing of IL-32 negated the 58% proliferation of ECs that occurred within 24 h in scrambled-transfected controls. Reduction of IL-32 neither affected apoptosis (insignificant changes in Bak-1, Bcl-2, Bcl-xL, lactate dehydrogenase, annexin V, and propidium iodide) nor VEGF or TGF-beta levels, but siIL-32-transfected adult and neonatal ECs produced up to 61% less NO, IL-8, and matrix metalloproteinase-9, and up to 3-fold more activin A and endostatin. In coculture-based angiogenesis assays, IL-32gamma dose-dependently increased tube formation up to 3-fold; an alphaVbeta3 inhibitor prevented this activity and reduced IL-32gamma-induced IL-8 by 85%. In matrigel plugs loaded with IL-32gamma, VEGF, or vehicle and injected into live mice, we observed the anticipated VEGF-induced increase in neocapillarization (8-fold versus vehicle), but unexpectedly, IL-32gamma was equally angiogenic. A second signal such as IFN-gamma was required to render cells responsive to exogenous IL-32gamma; importantly, this was confirmed using a completely synthetic preparation of IL-32gamma. In summary, we add angiogenic properties that are mediated by integrin alphaVbeta3 but VEGF-independent to the portfolio of IL-32, implicating a role for this versatile cytokine in pulmonary arterial hypertension and neoplastic diseases. |
| Databáze: | OpenAIRE |
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