High LDL-C levels attenuate onset of inflammation and cartilage destruction in antigen-induced arthritis.

Abstract:

OBJECTIVES:In this study, we used hypercholesterolaemic apolipoprotein E-deficient (Apoe-/-) mice to investigate LDL/oxLDL effect on synovial inflammation and cartilage destruction during antigen-induced arthritis (AIA). Further, as macrophage FcγRs are crucial to immune complex-mediated AIA, we investigated in vitro the effects of high cholesterol levels on the expression of FcγRs on macrophages. METHODS:AIA was induced by intra-articular injection of mBSA into knee joints of immunised Apoe-/- and wild type (WT) control mice. Joint swelling was measured by uptake of 99mTc pertechnetate (99mTc). Joint inflammation and cartilage destruction were assessed by histology. Anti-mBSA IgGs were measured by ELISA and specific T-cell response by lymphocyte stimulation test. Upon oxLDL stimulation of WT macrophages, protein levels of FcγRs were measured by flow cytometry. RESULTS:Local induction of AIA resulted in less joint swelling, synovial infiltrate and exudate in the joint cavity in Apoe-/- mice compared to WT controls, even though both their humoral and adaptive immune response were comparable. Whereas Apoe deficiency alone did not affect macrophage expression of FcγRs, oxLDL sharply reduced the protein levels of activating FcγRs, crucial in mediating cartilage damage. In agreement with the reduced inflammation in Apoe-/- mice, we observed decreased MMP activity and destruction in the articular cartilage. CONCLUSIONS:Taken together, our findings suggest that high levels of LDL/oxLDL during inflammation, dampen the initiation and chronicity of joint inflammation and cartilage destruction in AIA by regulating macrophage FcγR expression.

journal_name

Clin Exp Rheumatol

authors

Ascone G,Di Ceglie I,van den Bosch MHJ,Kruisbergen NNL,Walgreen B,Sloetjes AW,Lindhout E,Joosten LAB,van de Loo FAJ,Koenders MI,van der Kraan PM,Blom AB,van Lent PLEM

subject

Has Abstract

pub_date

2019-11-01 00:00:00

pages

983-993

issue

6

eissn

0392-856X

issn

1593-098X

pii

13702

journal_volume

37

pub_type

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