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J Immunol. 2017 Oct 15;199(8):2910-2920. doi: 10.4049/jimmunol.1700302. Epub 2017 Aug 30.

Cyclodextrin Reduces Cholesterol Crystal-Induced Inflammation by Modulating Complement Activation.

Author information

1
Center of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
2
Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, Rigshospitalet, 2100 Copenhagen, Denmark.
3
Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.
4
Department of Neurology, Oslo University Hospital Rikshospitalet, 0027 Oslo, Norway.
5
Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, 0424 Oslo, Norway.
6
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0318 Oslo, Norway.
7
K.G. Jebsen Inflammation Research Center, University of Oslo, 0318 Oslo, Norway.
8
Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, 0424 Oslo, Norway.
9
Institute of Innate Immunity, University Hospitals Bonn, 53127 Bonn, Germany.
10
Department of Immunology, Oslo University Hospital Rikshospitalet and University of Oslo, 0424 Oslo, Norway.
11
Research Laboratory, Nordland Hospital, 8092 Bodø, Norway; and.
12
K.G. Jebsen Thrombosis Research and Expertise Center, Institute of Clinical Medicine, University of Tromsø, 9037 Tromsø, Norway.
13
Center of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway; terje.espevik@ntnu.no.

Abstract

Cholesterol crystals (CC) are abundant in atherosclerotic plaques and promote inflammatory responses via the complement system and inflammasome activation. Cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (BCD) is a compound that solubilizes lipophilic substances. Recently we have shown that BCD has an anti-inflammatory effect on CC via suppression of the inflammasome and liver X receptor activation. The putative effects of BCD on CC-induced complement activation remain unknown. In this study, we found that BCD bound to CC and reduced deposition of Igs, pattern recognition molecules, and complement factors on CC in human plasma. Furthermore, BCD decreased complement activation as measured by terminal complement complex and lowered the expression of complement receptors on monocytes in whole blood in response to CC exposure. In line with this, BCD also reduced reactive oxygen species formation caused by CC in whole blood. Furthermore, BCD attenuated the CC-induced proinflammatory cytokine responses (e.g., IL-1α, MIP-1α, TNF, IL-6, and IL-8) as well as regulated a range of CC-induced genes in human PBMC. BCD also regulated complement-related genes in human carotid plaques treated ex vivo. Formation of terminal complement complex on other complement-activating structures such as monosodium urate crystals and zymosan was not affected by BCD. These data demonstrate that BCD inhibits CC-induced inflammatory responses, which may be explained by BCD-mediated attenuation of complement activation. Thus, these findings support the potential for using BCD in treatment of atherosclerosis.

PMID:
28855312
DOI:
10.4049/jimmunol.1700302
[Indexed for MEDLINE]
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