Interleukin-10 increases reverse cholesterol transport in macrophages through its bidirectional interaction with liver X receptor α

Bente Halvorsen; Sverre Holm; Arne Yndestad; Hanne Scholz; Ellen Lund Sagen; Hilde Nebb; Kirsten B Holven; Tuva B Dahl; Pål Aukrust

doi:10.1016/j.bbrc.2014.07.036

Interleukin-10 increases reverse cholesterol transport in macrophages through its bidirectional interaction with liver X receptor α

Biochem Biophys Res Commun. 2014 Aug 8;450(4):1525-30. doi: 10.1016/j.bbrc.2014.07.036. Epub 2014 Jul 15.

Authors

Bente Halvorsen¹, Sverre Holm², Arne Yndestad³, Hanne Scholz⁴, Ellen Lund Sagen², Hilde Nebb⁵, Kirsten B Holven⁶, Tuva B Dahl⁷, Pål Aukrust⁸

Affiliations

¹ Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; K.G. Jebsen Inflammation Research Center, University of Oslo, Oslo, Norway. Electronic address: Bente.Halvorsen@rr-research.no.
² Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
³ Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; K.G. Jebsen Inflammation Research Center, University of Oslo, Oslo, Norway.
⁴ Section for Transplantation, Institute for Surgical Research, Oslo University Hospital Rikshospitalet, Oslo, Norway.
⁵ Department of Nutrition, Institute for Basic Medical Sciences, University of Oslo, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁶ Department of Nutrition, Institute for Basic Medical Sciences, University of Oslo, Oslo, Norway.
⁷ Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁸ Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; K.G. Jebsen Inflammation Research Center, University of Oslo, Oslo, Norway.

PMID: 25035925
DOI: 10.1016/j.bbrc.2014.07.036

Abstract

Interleukin (IL)-10 is a prototypical anti-inflammatory cytokine that has been shown to attenuate atherosclerosis development. In addition to its anti-inflammatory properties, the anti-atherogenic effect of IL-10 has recently also been suggested to reflect a complex effect of IL-10 on lipid metabolism in macrophages. In the present study we examined the effects of IL-10 on cholesterol efflux mechanism in lipid-loaded THP-1 macrophages. Our main findings were: (i) IL-10 significantly enhanced cholesterol efflux induced by fetal-calf serum, high-density lipoprotein (HDL)2 and apolipoprotein A-1. (ii) The IL-10-mediated effects on cholesterol efflux were accompanied by an increased IL-10-mediated expression of the ATP-binding cassette transporters ABCA1 and ABCG1, that was further enhanced when the cells were co-activated with the liver X receptor (LXR)α agonist (22R)-hydroxycholesterol. (iii) The effect of LXRα activation on the IL-10-mediated effects on the ATP-binding cassette transporters seems to include enhancing effects on the IL-10 receptor 1 (IL10R1) expression and interaction with STAT-3 signaling. (iv) These enhancing effects on ABCA1 and ABCG1 was not seen when the cells were stimulated with the IL-10 family members IL-22 and IL-24. This study suggests that the anti-atherogenic properties of IL-10 may include enhancing effects on cholesterol efflux mechanism that involves cross-talk with LXRα activation.

Keywords: IL-10; LXR-α; Lipids; Macrophages; Reverse cholesterol transport.

MeSH terms

Biological Transport
Cell Line
Cholesterol / metabolism*
Humans
Interleukin-10 / physiology*
Liver X Receptors
Macrophages / metabolism*
Orphan Nuclear Receptors / metabolism*
Protein Binding
Real-Time Polymerase Chain Reaction

Substances

Liver X Receptors
NR1H3 protein, human
Orphan Nuclear Receptors
Interleukin-10
Cholesterol