title: Specific overexpression of tumour necrosis factor-α-induced protein (TNFAIP)9 in CD14(+) CD16(-) monocytes in patients with rheumatoid arthritis: comparative analysis with TNFAIP3.
abstract: The tumour necrosis factor (TNF)-α-induced proteins (TNFAIP)9 and TNFAIP3 play an important pathogenic role in murine arthritis. To clarify their pathophysiological roles in patients with rheumatoid arthritis (RA), we examined their expression and localization in peripheral blood mononuclear cells (PBMC). TNFAIP9 and TNFAIP3 mRNA expression was determined in PBMC of RA patients and healthy subjects (control). Flow cytometry was used to analyse the main TNFAIP9- and TNFAIP3-expressing cell populations. TNFAIP9 and TNFAIP3 mRNA expression levels were examined in vitro on CD14(+) cells stimulated with TNF-α and lipopolysaccharide (LPS). The expression levels of TNFAIP9 and TNFAIP3 mRNA were also measured before and 12 weeks after treatment with tocilizumab and abatacept. TNFAIP9 expression was significantly higher, while TNFAIP3 expression was lower in PBMC of RA (n=36) than the control (n=24) (each P < 0.05). TNFAIP9 was expressed on CD14(+) cells, especially in human leucocyte antigen D-related (HLA-DR)(+) CD14(bright) CD16(-) cells, while TNFAIP3 was expressed mainly on CD3(+) T cells. TNF-α and LPS induced TNFAIP9 and TNFAIP3 in human CD14(+) monocytes in vitro. Treatment with tocilizumab (n=13), but not abatacept (n=11), significantly reduced TNFAIP9 mRNA expression in PBMC, which was associated with reduction in the number of circulating CD14(bright) monocytes. The expression of TNFAIP9 in CD14(+) cells was specifically elevated in patients with RA, regulated by TNF-α and LPS, and suppressed by tocilizumab, while TNFAIP3 in PBMC showed different localization and induction patterns.
authors: Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba.|Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medicine and Dental Sciences, Niigata, Japan.
authors: C
authors: C
authors: Takai
authors: Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba.
authors: I
authors: I
authors: Matsumoto
authors: Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba.
authors: A
authors: A
authors: Inoue
authors: Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba.
authors: N
authors: N
authors: Umeda
authors: Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba.
authors: Y
authors: Y
authors: Tanaka
authors: Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba.
authors: Y
authors: Y
authors: Kurashima
authors: Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medicine and Dental Sciences, Niigata, Japan.
authors: Y
authors: Y
authors: Wada
authors: Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medicine and Dental Sciences, Niigata, Japan.
authors: I
authors: I
authors: Narita
authors: Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba.
authors: T
authors: T
authors: Sumida
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology*; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics; D010088:Oxidoreductases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D017452:Receptors, IgG / Q000378:metabolism; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D010088:Oxidoreductases; C503310:STEAP4 protein, human; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; C502936:tocilizumab
keywords: TNF-α-induced proteins; TNFAIP9; monocytes; pathogenesis; rheumatoid arthritis