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Cardioprotective cytokine interleukin-33 is up-regulated by statins in human cardiac tissue.
- Source :
-
Journal of cellular and molecular medicine [J Cell Mol Med] 2018 Dec; Vol. 22 (12), pp. 6122-6133. Date of Electronic Publication: 2018 Sep 14. - Publication Year :
- 2018
-
Abstract
- Interleukin (IL)-33 is a member of the IL-1 family and is able to act cardioprotective. The aim of this study was to investigate the regulation of IL-33 by 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitors (statins) and bisphosphonates (BPs) in human cardiac tissue. The lipophilic fluvastatin, simvastatin, atorvastatin, and lovastatin as well as the nitrogenous BPs alendronate and ibandronate, but not hydrophilic pravastatin increased IL-33 mRNA and intracellular IL-33 protein levels in both human adult cardiac myocytes (HACM) and fibroblasts (HACF). Additionally, fluvastatin reduced soluble ST2 secretion from HACM. IL-33 was also up-regulated by the general inhibitor of prenylation perillic acid, a RhoA kinase inhibitor Y-27632, and by latrunculin B, but statin-induced IL-33 expression was inhibited by mevalonate, geranylgeranyl pyrophosphate (GGPP) and RhoA activator U-46619. The IL-33 promoter was 2.3-fold more accessible in statin-treated HACM compared to untreated cells (P = 0.037). In explanted hearts of statin-treated patients IL-33 protein was up-regulated as compared with the hearts of non-statin-treated patients (P = 0.048). As IL-33 was previously shown to exert cardioprotective effects, one could speculate that such up-regulation of IL-33 expression in human cardiac cells, which might happen mainly through protein geranylgeranylation, could be a novel mechanism contributing to known cardioprotective effects of statins and BPs.<br /> (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)
- Subjects :
- 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid pharmacology
Amides pharmacology
Apoptosis drug effects
Bridged Bicyclo Compounds, Heterocyclic pharmacology
Cyclohexenes pharmacology
Cytokines genetics
Diphosphonates pharmacology
Fibroblasts drug effects
Fluvastatin pharmacology
Gene Expression Regulation drug effects
Heart Diseases drug therapy
Humans
Lovastatin pharmacology
Mevalonic Acid pharmacology
Monoterpenes pharmacology
Myocardium pathology
Myocytes, Cardiac drug effects
Myocytes, Cardiac metabolism
Pravastatin pharmacology
Pyridines pharmacology
Simvastatin pharmacology
Thiazolidines pharmacology
rhoA GTP-Binding Protein
Heart drug effects
Heart Diseases diet therapy
Interleukin-33 genetics
Myocardium metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1582-4934
- Volume :
- 22
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of cellular and molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 30216659
- Full Text :
- https://doi.org/10.1111/jcmm.13891