title: Interleukin-33 stimulates GM-CSF and M-CSF production by human endothelial cells.
abstract: Interleukin (IL)-33, a member of the IL-1 family of cytokines, is involved in various inflammatory conditions targeting amongst other cells the endothelium. Besides regulating the maturation and functions of myeloid cells, granulocyte macrophage-colony stimulating factor (GM-CSF) and macrophage-CSF (M-CSF) have been shown to play a role in such pathologies too. It was the aim of our study to investigate a possible influence of IL-33 on GM-CSF and M-CSF production by human endothelial cells. IL-33, but not IL-18 or IL-37, stimulated GM-CSF and M-CSF mRNA expression and protein production by human umbilical vein endothelial cells (HUVECs) and human coronary artery ECs (HCAECs) through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway in an IL-1-independent way. This effect was inhibited by the soluble form of ST2 (sST2), which is known to act as a decoy receptor for IL-33. The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor fluvastatin could also be shown to moderately reduce the IL-33-mediated effect on M-CSF, but not on GM-CSF expression. In addition, IL-33, IL-1β, GM-CSF and M-CSF were detected in endothelial cells of human carotid atherosclerotic plaques using immunofluorescence. Upregulation of GM-CSF and M-CSF production by human endothelial cells, an effect that appears to be mediated by NF-κB and to be independent of IL-1, may be an additional mechanism through which IL-33 contributes to inflammatory activation of the vessel wall.
authors.forename: Eliana
authors.initials: E
authors.lastname: Montanari
authors.forename: Stefan
authors.initials: S
authors.lastname: Stojkovic
authors.forename: Christoph
authors.initials: C
authors.lastname: Kaun
authors.forename: Christof E
authors.initials: CE
authors.lastname: Lemberger
authors.forename: Rainer
authors.initials: R
authors.lastname: de Martin
authors.forename: Sabine
authors.initials: S
authors.lastname: Rauscher
authors.forename: Marion
authors.initials: M
authors.lastname: Gröger
authors.forename: Gerald
authors.initials: G
authors.lastname: Maurer
authors.forename: Christoph
authors.initials: C
authors.lastname: Neumayer
authors.forename: Ihor
authors.initials: I
authors.lastname: Huk
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
authors.affiliation: Svitlana Demyanets, MD, PhD, Department of Laboratory Medicine, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria, Tel.: +43 1 40400 73516, Fax: +43 1 40400 73587, E-mail: svitlana.demyanets@meduniwien.ac.at.
authors.forename: Svitlana
authors.initials: S
authors.lastname: Demyanets
authors.forename: Johann
authors.initials: J
authors.lastname: Wojta
mesh_terms: D016893:Carotid Stenosis / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D000077340:Fluvastatin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D020382:Interleukin-18 / Q000378:metabolism / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism; D000067596:Interleukin-33 / Q000378:metabolism* / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C506536:IL33 protein, human; C508587:IL37 protein, human; D007211:Indoles; D018836:Inflammation Mediators; D007375:Interleukin-1; D020382:Interleukin-18; D053583:Interleukin-1beta; D000067596:Interleukin-33; D016328:NF-kappa B; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000077340:Fluvastatin; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: GM-CSF; Interleukin-33; M-CSF; ST2; endothelial cells