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The inflammatory mediator oncostatin M induces stromal derived factor-1 in human adult cardiac cells

P. J. Hohensinner^*,, C. Kaun^*, K. Rychli^*, A. Niessner^*, S. Pfaffenberger^*, G. Rega^*, A. Furnkranz, P. Uhrin, J. Zaujec, T. Afonyushkin, V. N. Bochkov, G. Maurer^*, K. Huber and J. Wojta^*,,1

^* Department of Internal Medicine II and

Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria;

Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria; and

Third Department of Medicine, Wilhelminenhospital, Vienna, Austria

¹Correspondence: Department of Internal Medicine II, Waehringer Guertel 18-20, Vienna, Austria. E-mail: johann.wojta{at}meduniwien.ac.at

Stromal derived factor 1 (SDF-1) is a CXC chemokine important in the homing process of stem cells to injured tissue. It has been implicated in healing and tissue repair. Growing evidence suggests that the glycoprotein-130 (gp130) ligand family is involved in repair processes in the heart. The aim of our study was to determine whether gp130 ligands could affect SDF-1 expression in cardiac cells. Human adult cardiac myocytes (HACMs) and fibroblasts (HACFs) were treated with gp130 ligands. Protein and mRNA levels of SDF-1 were determined using ELISA and RT-PCR, respectively. mRNA levels of SDF-1 were determined in human and mouse heart samples by RT-PCR. HACMs and HACFs constitutively express SDF-1, which was significantly up-regulated by the gp130 ligand oncostatin M (OSM). This effect was counteracted by a p38 inhibitor and to a lesser extent by a PI3K inhibitor. mRNA expression of SDF-1 in hearts of mice injected with OSM increased significantly. Levels of OSM and SDF-1 mRNA correlated significantly in human failing hearts. Our data, showing that OSM induces SDF-1 protein secretion in human cardiac cells in vitro and murine hearts in vivo, suggest that OSM via the induction of SDF-1 might play a key role in repair and tissue regeneration.—Hohensinner, P. J., Kaun, C., Rychli, K., Niessner, A., Pfaffenberger, S., Rega, G., Furnkranz, A., Uhrin, P., Zaujec, J., Afonyushkin, T., Bochkov, V. N., Maurer, G., Huber, K., Wojta, J. The inflammatory mediator oncostatin M induces stromal derived factor-1 in human adult cardiac cells.

Key Words: cytokine • heart