Background Decoy receptor 3 (DcR3) is a secreted decoy tumor necrosis factor receptor (TNFR) and competitively binds and inhibits the TNF family including Fas-ligand (FasL), LIGHT, and TL1A. DcR3 is overexpressed in tumor cells and might benefit tumors by helping them to avoid cytotoxic and regulatory effects of the ligands. We previously reported that DcR3 overexpressed in rheumatoid synovial fibroblasts (RA-FLS) stimulated by TNF-alpha protects the cells from Fas-induced apoptosis (1). Meanwhile, recent studies have suggested that DcR3 directly induces osteoclast formation from monocytes (2), and that DcR3 triggers enhanced adhesion of monocytes via reverse signalling (3,4). We recently reported that DcR3 binds to TL1A expressed on RA-FLS resulting in the negative regulation of cell proliferation induced by inflammatory cytokines (5). Therefore, DcR3 may regulate gene expressions in RA-FLS by binding to TL1A on RA-FLS as a ligand.
Objectives In the present study, we studied the genes expression profiles in RA-FLS regulated by DcR3.
Methods Four individual lines of primary cultured RA-FLS were incubated with either 1.0 μg/ml of recombinant human DcR3-Fc protein (DcR3-Fc) or control IgG1 for 12h. After the incubation, RNA was extracted and reverse-transcribed to cDNA. Gene expressions were detected by microarray assay (GeneChip® 3’ Expression Array, Affymetrix). The relative gene expression profiles in DcR3-stimulated cells and controls were analysed by AVADIS® software (Strand Life Sciences).
Results Microarray data analysis revealed that DcR3 up-regulates and down-regulates gene expression in RA-FLS. Among the most significantly regulated 100 genes by DcR3, 45 genes were up-regulated and 55 genes were down-regulated. The functions of up-regulated genes included protein complex assembly, cell motility, regulation of transcription, cellular protein catabolic process, cell membrane, nucleotide binding, and glycosylation. Meanwhile, those of down-regulated genes included transcription regulator activity, RNA biosynthetic process, cytoskeleton, zinc finger region, protein complex assembly, phosphate metabolic process, mitochondrion, ion transport, nucleotide binding, and cell fraction.
Conclusions In this study, we first revealed the gene expression profiles in RA-FLS regulated by DcR3. Combined with our previous findings, DcR3 may regulate the gene expression of various key molecules in RA-FLS by binding to TL1A and affect the pathogenesis of RA.
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Disclosure of Interest None Declared