The novel cytokine interleukin-36α is expressed in psoriatic and rheumatoid arthritis synovium
- Silke Frey1,
- Anja Derer1,
- Maria-Elena Messbacher1,
- Dominique L P Baeten2,
- Serena Bugatti3,
- Carlomaurizio Montecucco3,
- Georg Schett1,
- Axel J Hueber1
- 1Department of Internal Medicine 3 and Institute for Clinical Immunology, University Hospital of Erlangen-Nuremberg, Erlangen, Germany
- 2Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
- 3Division of Rheumatology, University of Pavia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
- 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;
- Received 26 June 2012
- Revised 30 November 2012
- Accepted 2 December 2012
- Published Online First 25 December 2012
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.