title: The effect of multimeric adiponectin isoforms and leptin on the function of rheumatoid fibroblast-like synoviocytes.
abstract: OBJECTIVE
  To evaluate the effects of physiologically relevant concentrations of multimeric adiponectin isoforms and leptin on the function of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA).
  
  
  METHODS
  FLS, isolated from the synovial tissue of 21 RA patients, were stimulated for 24 h with interleukin (IL)-1β (1 ng/mL) and adiponectin isoforms [fraction enriched with high-molecular-weight (HMW) oligomers and middle-molecular-weight (MMW) hexamers or low-molecular-weight (LMW) trimers, 10 μg/mL each], or leptin (10 ng/mL), either separately or in a combination of IL-1β and the respective adipokine. Moreover, cells were pre-treated for 24 h with adipokines, then stimulated for 8 h with IL-1β. The concentrations of IL-6, IL-8, matrix metalloproteinase (MMP)-3, and dickkopf (DKK)-1, an inhibitor of osteoblastogenesis, in culture supernatants, as well as the concentrations of leptin, HMW, MMW, and LMW adiponectin in sera and synovial fluid (SF) samples, were measured by specific enzyme-linked immunosorbent assays (ELISAs).
  
  
  RESULTS
  In comparison with sera, SF samples contained similar amounts of leptin, lower amounts of total adiponectin but a higher proportion of the LMW isoform. Separately added IL-1β and HMW/MMW adiponectin, but not LMW adiponectin or leptin, up-regulated the release of IL-6, IL-8, and MMP-3 from FLS but no synergy was observed in co-stimulation experiments. However, pre-treatment of FLS with HMW/MMW or LMW significantly raised the IL-1β-triggered secretion of MMP-3 and IL-6 or MMP-3, respectively.
  
  
  CONCLUSIONS
  Adiponectin not only triggers pro-inflammatory and pro-destructive activities of rheumatoid FLS but also pre-disposes these cells to a stronger response to IL-1β. Thus, it is likely that adiponectin is more important in the initiation phase than in the chronic phase of RA.
authors.affiliation: a Department of Pathophysiology and Immunology , Institute of Rheumatology , Warsaw , Poland.
authors.forename: E
authors.initials: E
authors.lastname: Kontny
authors.affiliation: a Department of Pathophysiology and Immunology , Institute of Rheumatology , Warsaw , Poland.
authors.forename: I
authors.initials: I
authors.lastname: Janicka
authors.affiliation: a Department of Pathophysiology and Immunology , Institute of Rheumatology , Warsaw , Poland.
authors.forename: U
authors.initials: U
authors.lastname: Skalska
authors.affiliation: a Department of Pathophysiology and Immunology , Institute of Rheumatology , Warsaw , Poland.
authors.forename: W
authors.initials: W
authors.lastname: Maśliński
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D008875:Middle Aged; D008970:Molecular Weight; D020033:Protein Isoforms / Q000494:pharmacology; D013583:Synovial Membrane / Q000473:pathology*
chemical_list: D052242:Adiponectin; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D020738:Leptin; D020033:Protein Isoforms; D019278:Matrix Metalloproteinase 3