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Extended report
The novel cytokine interleukin-36α is expressed in psoriatic and rheumatoid arthritis synovium
  1. Silke Frey1,
  2. Anja Derer1,
  3. Maria-Elena Messbacher1,
  4. Dominique L P Baeten2,
  5. Serena Bugatti3,
  6. Carlomaurizio Montecucco3,
  7. Georg Schett1,
  8. Axel J Hueber1
  1. 1Department of Internal Medicine 3 and Institute for Clinical Immunology, University Hospital of Erlangen-Nuremberg, Erlangen, Germany
  2. 2Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
  3. 3Division of Rheumatology, University of Pavia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
  1. Correspondence to Dr Axel J Hueber, Department of Internal Medicine 3 and Institute for Clinical Immunology, University Hospital of Erlangen-Nuremberg, Ulmenweg 18, Erlangen 90154, Germany; axel.hueber{at}uk-erlangen.de

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.

  • Cytokines
  • Arthritis
  • Inflammation

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