IL-33 reduces macrophage foam cell formation

McLaren, James E. ORCID: https://orcid.org/0000-0002-7021-5934, Michael, Daryn Robert, Salter, Rebecca Claire, Ashlin, Timothy Gordon, Calder, Claudia Jane, Miller, Ashley M., Liew, Foo Y. and Ramji, Dipak Purshottam ORCID: https://orcid.org/0000-0002-6419-5578 2010. IL-33 reduces macrophage foam cell formation. The Journal of Immunology 185 (2) , pp. 1222-1229. 10.4049/jimmunol.1000520

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Abstract

The development of atherosclerosis, a chronic inflammatory disease characterized by the formation of arterial fibrotic plaques, has been shown to be reduced by IL-33 in vivo. However, whether IL-33 can directly affect macrophage foam cell formation, a key feature of atherosclerotic plaques, has not been determined. In this study, we investigated whether IL-33 reduces macrophage foam cell accumulation in vivo and if IL-33 reduces their formation in vitro using THP-1 and primary human monocyte-derived macrophages. In Apolipoprotein E−/− mice fed on a high fat diet, IL-33 treatment significantly reduced the accumulation of macrophage-derived foam cells in atherosclerotic plaques. IL-33 also reduced macrophage foam cell formation in vitro by decreasing acetylated and oxidized low-density lipoprotein uptake, reducing intracellular total and esterified cholesterol content and enhancing cholesterol efflux. These changes were associated with IL-33–mediated reduction in the expression of genes involved in modified low-density lipoprotein uptake, such as CD36, and simultaneous increase in genes involved in cholesterol efflux, including Apolipoprotein E, thereby providing a mechanism for such an action for this cytokine. IL-33 also decreased the expression of key genes implicated in cholesterol esterification and triglyceride storage, including Acyl-CoA:cholesterol acyltransferase 1 and Adipocyte differentiation-related protein. Furthermore, using bone marrow-derived macrophages from ST2−/− mice, we demonstrate that the IL-33 receptor, ST2, is integral to the action of IL-33 on macrophage foam cell formation. In conclusion, IL-33 has a protective role in atherosclerosis by reducing macrophage foam cell formation suggesting that IL-33 maybe a potential therapeutic agent against atherosclerosis.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Psychology
Subjects:	Q Science > QH Natural history > QH301 Biology Q Science > QR Microbiology > QR180 Immunology R Medicine > RB Pathology
Publisher:	American Association of Immunologists
ISSN:	0022-1767
Last Modified:	17 Jan 2023 10:20
URI:	https://orca.cardiff.ac.uk/id/eprint/8948

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