Interleukin 32 promotes angiogenesis: a new role for a versatile cytokine. (P6266)
| Autor: | Ina Rudloff, Jarod Zepp, Hannah Dinkel, Brent Palmer, Laszlo Farkas, Carlyne Cool, Laima Taraseviciene-Stewart, Soo-Hyun Kim, Charles Dinarello, Norbert Voelkel, Claudia Nold, Marcel Nold |
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| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 190:46.4-46.4 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | IL-32 is a multi-faceted cytokine with roles in infection, autoimmunity and cancer. It aggravates inflammation, inhibits virus propagation and acts as a critical regulator of endothelial cell (EC) function. We now discovered that IL-32 also possesses angiogenic properties. The hyperproliferative EC of pulmonary hypertension and glioblastoma multiforme exhibited a markedly increased abundance of IL-32, and the cytokine colocalized with integrin αVβ3. In vitro, VEGF receptor blockade resulted in hyperproliferation of EC and a 3.4-fold increase in IL-32. When IL-32 was silenced by siRNA, the proliferation of adult and fetal EC was reduced (change in cell number +58% vs -15%). Mechanistic studies revealed that siIL-32-transfected EC produced 3-fold more activin A and angiopoietin 2, but 61% less NO, whereas neither apoptosis nor the abundance of VEGF or TGF-β were affected. Interestingly, pre-treatment with IFNγ was required to render EC responsive to exogenous IL-32γ. To obtain in vivo evidence for these angiogenic effects, we injected mice with matrigel plugs loaded with IL-32γ, VEGF or vehicle, and performed CD31- and H&E-staining after 14d. As anticipated, 25 ng/ml of VEGF increased neocapillarization 8-fold, but unexpectedly the effect of 100 ng/ml IL-32γ was even stronger (8.5-fold). In summary, we add VEGF-independent angiogenic properties to the portfolio of IL-32, implicating a role in pulmonary hypertension and neoplastic diseases that is possibly exerted via αVβ3. |
| Databáze: | OpenAIRE |
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