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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Publisher's URL: http://dx.doi.org/10.4049/jimmunol.1000520
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: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| 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: | 0022-1767 |
| ISSN (Online): | 1550-6606 |
| Published Online: | 11 June 2010 |
| Related URLs: |
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