Objective.Leukocyte immunoglobulin-like receptor A3 (LILRA3) belongs to a family of cell-surface receptors with inhibitory or activating functions. LILRA3 lacks transmembrane and cytoplasmic domains, suggesting that it may be secreted. LILRA3 has high homology to activating LILRA1 and A2, hence may act as a soluble agonist/antagonist to these receptors. Individuals lacking the LILRA3 gene have higher incidence of multiple sclerosis and Sjögren’s syndrome, suggesting LILRA3 may be antiinflammatory. LILRA3 mRNA was detected in monocytes and mast cells but no protein expression has ever been described. Our aim was to examine LILRA3 protein expression in serum and synovial fluid of patients with rheumatoid arthritis (RA) and determine its in vitro regulation.Methods.We developed a new ELISA to examine levels of LILRA3 in serum, synovial fluid, and/or culture supernatants from controls and patients with RA, degenerative arthritis, or gout. We used qRT-PCR and flow cytometry to determine the expression and cytokine-mediated regulation of LILRA3.Results.LILRA3 protein is constitutively present in normal serum, with significantly higher concentrations in patients with RA. Serum LILRA3 concentrations from RA patients correlated with disease activity and levels in synovial fluid. Treatment of monocytes with interleukin 10 or interferon-γ significantly upregulated while tumor necrosis factor-α significantly downregulated LILRA3 mRNA and protein expression.Conclusion.We show for the first time that LILRA3 is significantly increased in serum of patients with RA and is tightly regulated by key cytokines involved in pathogenesis of RA. These results suggest that LILRA3 may play a role in chronic inflammatory conditions such as RA.
Leishmanial lipid suppresses tumor necrosis factor α, interleukin-1β, and nitric oxide production by adherent synovial fluid mononuclear cells in rheumatoid arthritis patients and induces apoptosis through the mitochondrial-mediated pathway