Interleukin-33 Induces Expression of Adhesion Molecules and Inflammatory Activation in Human Endothelial Cells and in Human Atherosclerotic Plaques

• DOI: 10.1161/atvbaha.111.231431
• Publication Date: 2011-07-08T15:16:49Z
• Authors: Svitlana Demyanets; Viktoria Konya; Stefan P. Kastl; Christoph Kaun; Sabine Rauscher; Alexander Niessner; Richard Pentz; Stefan Pfaffenberger; Kathrin Rychli; Christof E. Lembe...; Rainer de Martin; Akos Heinemann; Ihor Huk; Marion Gröger; Gerald Maurer; Kurt Huber; Johann Wojta
• Keywords: Inflammation; 0303 health sciences; Interleukins; NF-kappa B; Endothelial Cells; Receptors, Cell Surface; Interleukin-33; Interleukin-1 Receptor-Like 1 Protein; Plaque, Atherosclerotic; 3. Good health; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Cell Adhesion; Leukocytes; Humans; Cell Adhesion Molecules; Cells, Cultured

Objective— Interleukin (IL)-33 is the most recently described member of the IL-1 family of cytokines and it is a ligand of the ST2 receptor. While the effects of IL-33 on the immune system have been extensively studied, the properties of this cytokine in the cardiovascular system are much less investigated.

Methods/Results— We show here that IL-33 promoted the adhesion of human leukocytes to monolayers of human endothelial cells and robustly increased vascular cell adhesion molecule-1, intercellular adhesion molecule-1, endothelial selectin, and monocyte chemoattractant protein-1 protein production and mRNA expression in human coronary artery and human umbilical vein endothelial cells in vitro as well as in human explanted atherosclerotic plaques ex vivo. ST2-fusion protein, but not IL-1 receptor antagonist, abolished these effects. IL-33 induced translocation of nuclear factor-κB p50 and p65 subunits to the nucleus in human coronary artery endothelial cells and human umbilical vein endothelial cells and overexpression of dominant negative form of IκB kinase 2 or IκBα in human umbilical vein endothelial cells abolished IL-33-induced adhesion molecules and monocyte chemoattractant protein-1 mRNA expression. We detected IL-33 and ST2 on both protein and mRNA level in human carotid atherosclerotic plaques.

Conclusion— We hypothesize that IL-33 may contribute to early events in endothelial activation characteristic for the development of atherosclerotic lesions in the vessel wall, by promoting adhesion molecules and proinflammatory cytokine expression in the endothelium.