Original Article Smooth muscle homeostasis in human atherosclerotic plaques through Interleukin 15 signalling
Jelger J. van der Meer, Onno J. de Boer, Peter Teeling, Chris M. van der Loos, Mark C. Dessing, Allard C. van der Wal
Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
Received March 10, 2011; accepted March 18, 2011; Epub March 22; published March 31, 2011
Abstract: Interleukin (Il)-15 is a cytokine that has a broad tissue distribution and is important in maintaining homeostasis of cells and stability of tissues. When Il-15 is also expressed by vascular smooth muscle cells (SMC), which are the dominant type of cells in most atherosclerotic plaques, it could be important in maintaining plaque tissue integrity and hence resistance of plaques towards development of clinically relevant complications such as plaque rupture and thrombosis. In this study, Il-15 and Il-15Rα in vitro expression by coronary artery SMC was investigated using RT-PCR and FACS analysis. Immunohistochemistry was used to study in situ expression of Il-15 and Il-15R by SMC of human carotid artery atherosclerotic plaques. Multiplex ligand-dependent probe amplification (MLPA) was used to investigate the mRNA expression of 40 pro- and anti inflammatory genes after stimulating coronary SMC with Il-15. We found that atherosclerotic SMC express both Il- 15 and its receptor Il-15R, and IFN-γ and TNF-α enhance Il-15R expression in cultured SMC. MLPA studies on SMC revealed enhanced expression of PDGF beta mRNA after Il15 stimulation. In conclusion, our data suggest that IL-15 may contribute to atherosclerotic plaque integrity by stimulation of smooth muscle cells, probably in a PDGF dependent fashion. (IJCEP1103005).
Address all correspondence to: Dr. Allard C van der Wal Department of Pathology, Academic Medical Center Meibergdreef 9,1105AZ Amsterdam, the Netherlands. Tel: +31 (0)20-566 5633. Fax: +31 (0)20-566 9523. E-mail: a.c.vanderwal@amc.uva.nl