Interferon-alpha prevents apoptosis of endothelial cells after short-term exposure but induces replicative senescence after continuous stimulation.

Pammer J, Reinisch C, Birner P, Pogoda K, Stürzl M, Tschachler E (2006)

Publication Status: Published

Publication Type: Journal article

Publication year: 2006

Journal

Laboratory Investigation Nature Publishing Group: Open Access Hybrid Model Option B

Book Volume: 86

Pages Range: 997-1007

Journal Issue: 10

DOI: 10.1038/labinvest.3700461

Abstract

Although the antiangiogenic activity of type I interferons (IFN) is well known, the mechanism by which it occurs is unclear. In the present study, we have investigated effects of short-term and long-term IFN-alpha exposure on different types of endothelial cells (EC). Short-term IFN-alpha treatment resulted in a distinct reduction of apoptosis of serum and growth factor starved HUVEC and HDMEC. This was accompanied by a strong upregulation of the IFN inducible guanylate binding protein-1 (GBP-1) whereas no consistent regulation of several known antiapoptotic proteins was evident. Stable transfection of HUVEC with an expression vector for GBP-1 mimicked the protective effect of IFN-alpha, suggesting that GBP-1 may contribute to the inhibition of apoptosis. When IFN-alpha, together with serum and EC growth factors, was present continuously a decrease of population doublings by more than 40% was observed in both HDMEC and HCAEC. In addition, the cells displayed a senescent phenotype significantly earlier than control cells and showed an increased adherence for monocytes. Our findings suggest that the antiangiogenic effect of IFN-alpha is mediated by inducing EC senescence rather than EC apoptosis. Furthermore IFN-alpha released in chronic inflammatory conditions might contribute via its prosenescent activity to the pathogenesis of atherosclerosis.

Authors with CRIS profile

Michael Stürzl Professur für Molekulare und Experimentelle Chirurgie

Involved external institutions

Medizinische Universität Wien

Austria (AT) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich

Germany (DE)

How to cite

APA:

Pammer, J., Reinisch, C., Birner, P., Pogoda, K., Stürzl, M., & Tschachler, E. (2006). Interferon-alpha prevents apoptosis of endothelial cells after short-term exposure but induces replicative senescence after continuous stimulation. Laboratory Investigation, 86(10), 997-1007. https://doi.org/10.1038/labinvest.3700461

MLA:

Pammer, Johannes, et al. "Interferon-alpha prevents apoptosis of endothelial cells after short-term exposure but induces replicative senescence after continuous stimulation." Laboratory Investigation 86.10 (2006): 997-1007.

BibTeX: Download