title: Comparison of rheumatoid articular adipose and synovial tissue reactivity to proinflammatory stimuli: contribution to adipocytokine network.
abstract: OBJECTIVE
  (1) To compare spontaneous and stimuli-induced adipocytokine secretion by articular adipose tissue (AAT) and synovial membrane (SM) explants obtained from patients with rheumatoid arthritis (RA). (2) To investigate the biological activity of AAT and SM released factors.
  
  
  METHODS
  Tissues were obtained from patients undergoing joint replacement surgery. Tissue explants were treated with proinflammatory cytokines relevant to RA pathogenesis (interleukin 1β (IL-1β), tumour necrosis factor (TNF), interferon γ, IL-15, IL-17, IL-23). Selected adipocytokine (TNF, IL-6, IL-8, IL-1β, IL-1Ra, adiponectin, leptin) concentrations were measured in culture supernatants using ELISA. The biological activity of tissue-conditioned media was evaluated by measuring production of selected factors (IL-6, IL-8, Dickkopf-1, osteoprotegerin) by fibroblast-like synoviocytes (FLS).
  
  
  RESULTS
  Spontaneous cytokine release from AAT was ≤12% of that produced by SM, while leptin was secreted in similar amounts. AAT was highly reactive to proinflammatory cytokines (IL-1β>TNF). AAT treated with IL-1β released four times more leptin, similar amounts of IL-6 and IL-8 and about 20% of TNF, as compared with SM. Upon activation, the IL-1 receptor antagonist (IL-1Ra)/IL-1β ratio was higher in AAT than in SM cultures. Irrespective of activation status, SM produced twice as much adiponectin as AAT. Conditioned media from AAT and SM cultures similarly upregulated IL-6, IL-8, Dickkopf-1 and osteoprotegerin production by rheumatoid FLS.
  
  
  CONCLUSIONS
  Rheumatoid AAT is highly reactive tissue which upon stimulation secretes considerable amounts of proinflammatory (IL-6, IL-8, TNF) and anti-inflammatory (IL-1Ra) cytokines and classical adipokines. This tissue releases biologically active factors that intensify pathogenic activities of rheumatoid FLS. Thus, AAT should be considered an important contributor to the pathological processes taking place in the RA joint.
authors: Department of Pathophysiology and Immunology, Institute of Rheumatology, Warsaw, Poland. ewa.kontny@wp.pl
authors: Ewa
authors: E
authors: Kontny
authors: Magdalena
authors: M
authors: Plebanczyk
authors: Barbara
authors: B
authors: Lisowska
authors: Malgorzata
authors: M
authors: Olszewska
authors: Pawel
authors: P
authors: Maldyk
authors: Wlodzimierz
authors: W
authors: Maslinski
mesh_terms: D054392:Adipokines / Q000096:biosynthesis*; D000273:Adipose Tissue / Q000276:immunology*; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D019645:Arthroplasty, Replacement, Knee; D002358:Cartilage, Articular / Q000276:immunology*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013583:Synovial Membrane / Q000276:immunology* / Q000473:pathology; D046509:Tissue Culture Techniques
chemical_list: D054392:Adipokines; D017077:Culture Media, Conditioned; D016207:Cytokines; D018836:Inflammation Mediators