title: Decoy receptor 3 regulates the expression of various genes in rheumatoid arthritis synovial fibroblasts.
abstract: Decoy receptor 3 (DcR3), a member of the tumor necrosis factor (TNF) receptor (TNFR) superfamily, lacks the transmembrane domain of conventional TNFRs in order to be a secreted protein. DcR3 competitively binds and inhibits members of the TNF family, including Fas ligand (FasL), LIGHT and TNF-like ligand 1A (TL1A). We previously reported that TNFα-induced DcR3 overexpression in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) protects cells from Fas-induced apoptosis. Previous studies have suggested that DcR3 acting as a ligand directly induces the differentiation of macrophages into osteoclasts. Furthermore, we reported that DcR3 induces very late antigen-4 (VLA--4) expression in THP-1 macrophages, inhibiting cycloheximide-induced apoptosis and that DcR3 binds to membrane-bound TL1A expressed on RA-FLS, resulting in the negative regulation of cell proliferation induced by inflammatory cytokines. In the current study, we used cDNA microarray to search for genes in RA-FLS whose expression was regulated by the ligation of DcR3. The experiments revealed the expression profiles of genes in RA-FLS regulated by DcR3. The profiles showed that among the 100 genes most significantly regulated by DcR3, 45 were upregulated and 55 were downregulated. The upregulated genes were associated with protein complex assembly, cell motility, regulation of transcription, cellular protein catabolic processes, cell membrane, nucleotide binding and glycosylation. The downregulated genes were associated with transcription regulator activity, RNA biosynthetic processes, cytoskeleton, zinc finger region, protein complex assembly, phosphate metabolic processes, mitochondrion, ion transport, nucleotide binding and cell fractionation. Further study of the genes detected in the current study may provide insight into the pathogenesis and treatment of rheumatoid arthritis by DcR3-TL1A signaling.
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Chuo, Kobe, Hyogo 650-0017, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Fukuda
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miura
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Maeda
authors.forename: Masayasu
authors.initials: M
authors.lastname: Takahashi
authors.forename: Shinya
authors.initials: S
authors.lastname: Hayashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurosaka
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D016000:Cluster Analysis; D015536:Down-Regulation; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology*; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010010:Osteoclasts / Q000378:metabolism; D012313:RNA / Q000235:genetics; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013583:Synovial Membrane / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D059467:Transcriptome; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D053323:Receptors, Tumor Necrosis Factor, Member 6b; C505911:TNFRSF6B protein, human; C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D014409:Tumor Necrosis Factor-alpha; D012313:RNA