title: Smooth muscle homeostasis in human atherosclerotic plaques through interleukin 15 signalling.
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 II-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 TNF-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.
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jelger J
authors.initials: JJ
authors.lastname: van der Meer
authors.forename: Onno J
authors.initials: OJ
authors.lastname: de Boer
authors.forename: Peter
authors.initials: P
authors.lastname: Teeling
authors.forename: Chris M
authors.initials: CM
authors.lastname: van der Loos
authors.forename: Mark C
authors.initials: MC
authors.lastname: Dessing
authors.forename: Allard C
authors.initials: AC
authors.lastname: van der Wal
mesh_terms: D003331:Coronary Vessels / Q000378:metabolism*; D005434:Flow Cytometry; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D019409:Interleukin-15 / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D053647:Receptors, Interleukin-15 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D019409:Interleukin-15; D010982:Platelet-Derived Growth Factor; D053647:Receptors, Interleukin-15; D014409:Tumor Necrosis Factor-alpha