Interleukin-12B is upregulated by decoy receptor 3 in rheumatoid synovial fibroblasts

• Published in: Molecular medicine reports Vol. 13; no. 4; pp. 3647 - 3652
• Main Authors: FUKUDA, KOJI, MIURA, YASUSHI, MAEDA, TOSHIHISA, HAYASHI, SHINYA, KUROSAKA, MASAHIRO
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01-04-2016; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Aged; Antibodies - pharmacology; Apoptosis; Arthritis, Rheumatoid - pathology; Autoimmune diseases; Blotting, Western; Care and treatment; Cells, Cultured; Cytokines; decoy receptor 3; Development and progression; FasL protein; Feedback; Female; fibroblast-like synoviocytes; Fibroblasts; Fibroblasts - cytology; Fibroblasts - metabolism; Gene expression; Genetic aspects; Glycoprotein D; Health aspects; Humans; Immunoglobulin Fc Fragments - genetics; Immunoglobulin Fc Fragments - metabolism; Inflammation; Inflammatory bowel disease; Interleukin 12; Interleukin 23; Interleukin-12 Subunit p40 - genetics; Interleukin-12 Subunit p40 - metabolism; interleukin-12B; Interleukins; Ligands; Lymphocytes T; Lymphotoxin; Male; Medical research; Messenger RNA; Middle Aged; Osteoarthritis; p40 Protein; Properties; Protein expression; Proteins; Real-Time Polymerase Chain Reaction; Receptors, Tumor Necrosis Factor, Member 6b - genetics; Receptors, Tumor Necrosis Factor, Member 6b - metabolism; Recombinant Fusion Proteins - biosynthesis; Recombinant Fusion Proteins - isolation & purification; Recombinant Fusion Proteins - pharmacology; Rheumatoid arthritis; RNA, Messenger - metabolism; Studies; Synovial Membrane - cytology; Synoviocytes; Tumor Necrosis Factor Ligand Superfamily Member 15 - immunology; Tumor necrosis factor-TNF; Up-Regulation - drug effects; United States > US
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2016.4985

Decoy receptor 3 (DcR3) competitively binds to three ligands, Fas ligand, lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells and tumor necrosis factor-like ligand 1A (TL1A), to prevent their effects. Recent studies have suggested that DcR3 directly affects cells as a ligand. Using a microarray assay, our group newly identified interleukin (IL)-12B, which encodes the p40 subunit common to IL-12 and IL-23, as one of the genes for which expression in fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA-FLS) is induced by DcR3. The present study demonstrated that IL-12B mRNA expression was upregulated by DcR3-Fc in RA-FLS in a dose-dependent manner, but not in OA-FLS. IL-12B p40 protein in RA-FLS was increased when stimulated with DcR3-Fc. Pre-treatment with anti-TL1A antibody suppressed the upregulation of IL-12B mRNA in RA-FLS stimulated with DcR3-Fc. DcR3 mRNA expression in RA-FLS was induced by IL-23, but not by IL-12. These results indicated that DcR3 may increase IL-12 or IL-23 by inducing IL-12B p40 expression via membrane-bound TL1A on RA-FLS and that IL-23 reciprocally induces DcR3 expression in RA-FLS. DcR3 and IL-23 may interact in a feedback loop that aggravates local inflammation in patients with RA.