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AB0125 A crucial role for lectin-like oxidized LDL receptor-1 signal on synovial inflammation in RA
  1. H. Ito1,
  2. M. Ishikawa2,
  3. M. Akiyoshi2,
  4. K. Murata2,
  5. S. Tanida2,
  6. H. Shibuya2,
  7. T. Kasahara2,
  8. H. Yoshitomi3,
  9. T. Nakamura2
  1. 1Department of The Control For Rheumatic Diseases
  2. 2Department of Orthopaedic Surgery
  3. 3Kyoto University Graduate School of Medicine, Kyoto, Japan

Abstract

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 Declared

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