A CRUCIAL ROLE FOR LECTIN-LIKE OXIDIZED LDL RECEPTOR-1 SIGNAL ON SYNOVIAL INFLAMMATION IN RA

Background: LOX-1 (Lectin-like oxidized LDL receptor 1), one of functional receptors for oxidized LDL (ox-LDL), is expressed in various cells and its expression is enhanced by oxidative stress and inflammatory cytokines. However, little is known whether LOX-1 is expressed in the RA synovium or synovial cells and whether soluble form of LOX-1 (sLOX-1) has any potential diagnostic roles in human RA. Objectives: To determine whether LOX-1 and sLOX-1 are novel target molecules for the diagnosis and the treatment of RA. Methods: Human RA synovium and fibroblast-like synoviocytes (FLSs) were assessed for the expression of LOX-1 and production of MMP-1 and MMP-3 induced by ox-LDL.Levels of sLOX-1 in plasma and in synovial fluid were determined by a specific ELISA.Ox-LDL was injected intoknee joints of mice with or without an anti-LOX-1 neutralizing antibody or sLOX-1. Results: The ox-LDL and LOX-1 protein were presentin the synovialtissues in RA joints. The production of MMP-1 and MMP-3 were enhanced by the stimulation of FLSs with ox-LDL and were inhibited by blockade of ox-LDL–LOX-1 interaction with an anti-LOX-1 neutralizing antibody or sLOX-1. sLOX-1 levels were significantly higher in the plasma and synovial fluid of RA patients compared withosteoarthritispatients and healthy controls,andwere positively correlated withinflammatory markers and with disease activity of RA. Blockade of ox-LDL–LOX-1 interaction suppressed arthritic changesand MMP-3 expressioninduced by ox-LDLin the knees of mice. Conclusions: These findings strongly indicate that sLOX-1 is a novel biomarker for the diagnosis and the evaluation of disease activity of RA, and that LOX-1 may be a potent therapeutic target for RA. Disclosure of Interest: None DeclaredCitation: Annals of the Rheumatic Diseases, volume 71, supplement 3, year 2012, page 644Session: Cartilage, synovium and osteoimmunology (Abstracts accepted for publication )