title: Interleukin‑12B is upregulated by decoy receptor 3 in rheumatoid synovial fibroblasts.
abstract: 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.
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650‑0017, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Fukuda
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650‑0017, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miura
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650‑0017, Japan.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Maeda
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650‑0017, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Hayashi
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650‑0017, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurosaka
mesh_terms: D000368:Aged; D000906:Antibodies / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000473:pathology; D015153:Blotting, Western; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D013583:Synovial Membrane / Q000166:cytology; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000906:Antibodies; D007141:Immunoglobulin Fc Fragments; D053762:Interleukin-12 Subunit p40; D012333:RNA, Messenger; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D011993:Recombinant Fusion Proteins; C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15