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

Autor:	Ascone G; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., Di Ceglie I; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., van den Bosch MHJ; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., Kruisbergen NNL; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., Walgreen B; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., Sloetjes AW; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., Lindhout E; Future Diagnostics Solutions (FDx), Wijchen, the Netherlands., Joosten LAB; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands., van de Loo FAJ; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., Koenders MI; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., van der Kraan PM; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., Blom AB; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands., van Lent PLEM; Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands. peter.vanlent@radboudumc.nl.
Jazyk:	angličtina
Zdroj:	Clinical and experimental rheumatology [Clin Exp Rheumatol] 2019 Nov-Dec; Vol. 37 (6), pp. 983-993. Date of Electronic Publication: 2019 May 07.
Abstrakt:	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.
Databáze:	MEDLINE
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