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Modulation of autoimmune arthritis severity in mice by Apolipoprotein E (ApoE) and cholesterol

Abstract: Apolipoprotein E (ApoE) deficiency promoted an exacerbation of autoimmune arthritis in mice by inducing pro-inflammatory immune responses. In this study we analysed the contribution of hypercholesterolemia and/or the absence of ApoE anti-inflammatory properties, unrelated to its function in the control of cholesterol metabolism, towards the acceleration of arthritis in these mutant animals. The induction and severity of collagen type II-induced arthritis (CIA) were compared for B10.RIII wild type (WT), B10.RIII.ApoE+/- , B10.RIII.ApoE-/- and B10.RIII.LDLR-/- mice with different concentrations of circulating ApoE and cholesterol. A 50-70% reduction in serum levels of ApoE was observed in heterozygous B10.RIII.ApoE+/- mice in comparison to B10.RIII.WT, although both strains of mice exhibited similar circulating lipid profiles. This ApoE reduction was associated with an increased CIA severity that remained lower than in homozygous B10.RIII.ApoE-/- mice. An important rise in circulating ApoE concentration was observed in hypercholesterolemic B10.RIII.LDLR-/- mice fed with a normal chow diet, and both parameters further increased with an atherogenic hypercholesterolemic diet. However the severity of CIA in B10.RIII.LDLR-/- mice was similar to that of B10.RIII.WT controls. In conclusion, by comparing the evolution of CIA between several strains of mutant mice with different levels of serum ApoE and cholesterol, our results demonstrate that both hypercholesterolemia and ApoE regulate the intensity of in vivo systemic autoimmune responses. This article is protected by copyright. All rights reserved

 Fuente: Clinical and Experimental Immunology, 2016, 186(3), 292-303

 Publisher: Wiley-Blackwell

 Year of publication: 2016

 No. of pages: 32

 Publication type: Article

 DOI: 10.1111/cei.12857

 ISSN: 0009-9104,1365-2249

 Publication Url: http://onlinelibrary.wiley.com/doi/10.1111/cei.12857/abstract

Authorship

PILAR ALVAREZ SAINZ DE LA MAZA

GENRE, FERNANDA

IGLESIAS LOZANO, MARCOS

AUGUSTIN RODRÍGUEZ, JUAN JESÚS

ESCOLÁ GIL, JOAN CARLES

BLANCO VACA, FRANCISCO