title: Resistin Gene Expression is Downregulated in CD4(+) T Helper Lymphocytes and CD14(+) Monocytes in Rheumatoid Arthritis Responding to TNF-α Inhibition.
abstract: Rheumatoid arthritis (RA) is caused by complex interactions between immune cells and sustained by Th1 response cytokines. Resistin [resistance to insulin; (RETN)] is an inflammatory cytokine, first discovered in murine adipocytes. In man, RETN is mainly secreted by monocytes. The distinct role of RETN in the immune reaction is uncertain; however, RETN has pro-inflammatory, pro-fibrotic and possibly tolerogenic properties. The aim was to assess the reaction of RETN gene expression to TNF-α inhibition (I) in pathogenetic immune cell subsets in RA, in the context of Th1, inflammatory and regulatory cytokine gene expressions. Accordingly, we measured RETN, IFN-γ, TNF-β, IL-1β, TNF-α, TGF-β and IL-10 gene expressions in CD14(+) monocytes, CD4(+) T helper (Th) lymphocytes (ly), CD8(+) T cytotoxic (Tc) ly and CD19(+) B ly in active RA before and 3 months after start of TNF-αI. Leucocyte subsets were separated by specific monoclonal antibody-covered beads, RNA extracted and levels of RETN, Th1 response, inflammatory and regulatory cytokine mRNAs measured by quantitative reverse transcription-polymerase chain reaction technique. We found that TNF-αI caused a significant downregulation of RETN gene expression in CD14(+) monocytes and CD4(+) Th ly and was unchanged in CD8(+) Tc ly and CD19(+) B ly. Both in active RA and during TNF-αI, RETN mRNA levels were significantly higher in CD14(+) monocytes than in all other examined cell types. In monocytes, fold change in RETN and TGF-β gene expressions upon TNF-αI correlated significantly. Our findings indicate that RETN has pro-inflammatory as well as proresolving roles in active RA.
authors.affiliation: Division of Clinical Immunology, Department of Clinical Microbiology, Norrland's University Hospital, Umeå, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Nagaev
authors.affiliation: Department of Medicine, North Denmark Regional Hospital/Department of Health Science and Technolgy, University of Aalborg, Aalborg, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Andersen
authors.affiliation: Department of Medicine, North Denmark Regional Hospital/Department of Health Science and Technolgy, University of Aalborg, Aalborg, Denmark.
authors.forename: M K
authors.initials: MK
authors.lastname: Olesen
authors.affiliation: Division of Clinical Immunology, Department of Clinical Microbiology, Norrland's University Hospital, Umeå, Sweden.
authors.forename: O
authors.initials: O
authors.lastname: Nagaeva
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Wikberg
authors.affiliation: Division of Clinical Immunology, Department of Clinical Microbiology, Norrland's University Hospital, Umeå, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Mincheva-Nilsson
authors.affiliation: Department of Rheumatology, North Denmark Regional Hospital/Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. grethe.andersen.2@rn.dk.
authors.forename: G N
authors.initials: GN
authors.lastname: Andersen
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use*; D000328:Adult; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D052243:Resistin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology
chemical_list: D018941:Antigens, CD19; D018501:Antirheumatic Agents; C000604811:CD19 molecule, human; D015704:CD4 Antigens; C573415:IFNG protein, human; C508609:IL10 protein, human; C508585:IL1B protein, human; D053583:Interleukin-1beta; D018950:Lipopolysaccharide Receptors; D008233:Lymphotoxin-alpha; C499624:RETN protein, human; D052243:Resistin; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D000068879:Adalimumab