title: The novel cytokine interleukin-36α is expressed in psoriatic and rheumatoid arthritis synovium.
abstract: BACKGROUND
  Interleukin (IL)-36α is a recently described member of the IL-1 cytokine family with pro-inflammatory and clearly pathogenic properties in psoriasis.
  
  
  OBJECTIVE
  To determine the IL-36α expression in psoriatic arthritis (PsA) compared to rheumatoid arthritis (RA) and osteoarthritis (OA).
  
  
  METHODS
  Synovial tissues obtained from arthritis patients were stained for IL-36α, IL-36 receptor (IL-36R) and IL-36R antagonist (IL-36Ra) by immunohistochemistry and immunofluorescence. Lysates were examined for IL-36α by western blot analysis. Synovial fibroblasts (FLS) cultured in the presence of IL-36α were assayed for cytokine expression by quantitative real time PCR and multiplex assay. IL-36α-induced signal transduction in FLS was analysed by immunoblotting.
  
  
  RESULTS
  Expression of IL-36R and its ligands IL-36α and IL-36Ra was detected in the synovial lining layer and cellular infiltrates of patients with inflammatory arthritis. IL-36α was expressed significantly higher in PsA and RA than in OA synovium. CD138-positive plasma cells were identified as the main cellular source of IL-36α. No differences were observed for the expression of IL-36R and IL-36Ra between PsA, RA and OA. Functionally, IL-36α induced the expression of IL-6 and IL-8 in FLS through p38/NFkB activation.
  
  
  CONCLUSIONS
  IL-36α is up-regulated in PsA and RA synovium, expressed by tissue plasma cells and leads to IL-6 and IL-8 production by synovial fibroblasts. Hence, IL-36α links plasma cells to inflammatory cytokine production by FLS and may represent a key link between autoimmunity and the induction of synovitis.
authors.affiliation: Department of Internal Medicine 3 and Institute for Clinical Immunology, University Hospital of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Frey
authors.forename: Anja
authors.initials: A
authors.lastname: Derer
authors.forename: Maria-Elena
authors.initials: ME
authors.lastname: Messbacher
authors.forename: Dominique L P
authors.initials: DL
authors.lastname: Baeten
authors.forename: Serena
authors.initials: S
authors.lastname: Bugatti
authors.forename: Carlomaurizio
authors.initials: C
authors.lastname: Montecucco
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.forename: Axel J
authors.initials: AJ
authors.lastname: Hueber
mesh_terms: D000368:Aged; D015535:Arthritis, Psoriatic / Q000378:metabolism* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000473:pathology; D013583:Synovial Membrane / Q000378:metabolism*
chemical_list: C508586:IL36A protein, human; D007375:Interleukin-1