IL-33 Reduces Macrophage Foam Cell Formation

McLaren, J. E., Michael, D. R., Salter, R. C., Ashlin, T. G., Calder, C. J., Miller, A. M., Liew, F. Y. and Ramji, D. P. (2010) IL-33 Reduces Macrophage Foam Cell Formation. Journal of Immunology, 185(2), pp. 1222-1229. (doi: 10.4049/jimmunol.1000520)

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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:Articles
Glasgow Author(s) Enlighten ID:Liew, Prof Foo and Miller, Dr Ashley
Authors: McLaren, J. E., Michael, D. R., Salter, R. C., Ashlin, T. G., Calder, C. J., Miller, A. M., Liew, F. Y., and Ramji, D. P.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Journal of Immunology
Journal Abbr.:J. Immunol.
Publisher:American Association of Immunologists
ISSN (Online):1550-6606
Published Online:11 June 2010
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
486461The role of IL-35 in infection and inflammationFoo LiewMedical Research Council (MRC)G0801198Infection Immunity and Inflammation Medicine