Conflicting vascular and metabolic impact of the IL-33/sST2 axis.
Booz, George W
Zouein, Fouad A
Oxford University Press (OUP)
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Altara, R., Ghali, R., Mallat, Z., Cataliotti, A., Booz, G. W., & Zouein, F. A. (2018). Conflicting vascular and metabolic impact of the IL-33/sST2 axis.. Cardiovasc Res, 114 (12), 1578-1594. https://doi.org/10.1093/cvr/cvy166
Interleukin 33 (IL-33), which is expressed by several immune cell types, endothelial and epithelial cells, and fibroblasts, is a cytokine of the IL-1 family that acts both intra- and extracellularly to either enhance or resolve the inflammatory response. Intracellular IL-33 acts in the nucleus as a regulator of transcription. Once released from cells by mechanical stress, inflammatory cytokines, or necrosis, extracellular IL-33 is proteolytically processed to act in an autocrine/paracrine manner as an 'alarmin' on neighbouring or various immune cells expressing the ST2 receptor. Thus, IL-33 may serve an important role in tissue preservation and repair in response to injury; however, the actions of IL-33 are dampened by a soluble form of ST2 (sST2) that acts as a decoy receptor and is produced by endothelial and certain immune cells. Accumulating evidence supports the conclusion that sST2 is a biomarker of vascular health with diagnostic and/or prognostic value in various cardiovascular diseases, including coronary artery disease, myocardial infarction, atherosclerosis, giant-cell arteritis, acute aortic dissection, and ischaemic stroke, as well as obesity and diabetes. Although sST2 levels are positively associated with cardiovascular disease severity, the assumption that IL-33 is always beneficial is naïve. It is increasingly appreciated that the pathophysiological importance of IL-33 is highly dependent on cellular and temporal expression. Although IL-33 is atheroprotective and may prevent obesity and type 2 diabetes by regulating lipid metabolism, IL-33 appears to drive endothelial inflammation. Here, we review the current knowledge of the IL-33/ST2/sST2 signalling network and discuss its pathophysiological and translational implications in cardiovascular diseases.
Endothelial Cells, Immune System, Animals, Humans, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Obesity, Inflammation, Inflammation Mediators, Cell Communication, Signal Transduction, Lipid Metabolism, Biomarkers, Interleukin-33, Interleukin-1 Receptor-Like 1 Protein
British Heart Foundation (RG/15/11/31593)
British Heart Foundation (PG/15/99/31865)
External DOI: https://doi.org/10.1093/cvr/cvy166
This record's URL: https://www.repository.cam.ac.uk/handle/1810/283043