The novel cytokine interleukin-36α is expressed in psoriatic and rheumatoid arthritis synovium

Silke Frey, Anja Derer, Maria Elena Messbacher, Dominique L P Baeten, Serena Bugatti, Carlomaurizio Montecucco, Georg Schett, Axel J. Hueber

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1569-1574
Number of pages6
JournalAnnals of the Rheumatic Diseases
Volume72
Issue number9
DOIs
Publication statusPublished - Sep 2013

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Psoriatic Arthritis
Synovial Membrane
Interleukins
Rheumatoid Arthritis
Cytokines
Fibroblasts
Plasma Cells
Osteoarthritis
Interleukin-8
Plasmas
Arthritis
Interleukin-6
Interleukin Receptors
Tissue
Signal transduction
Synovitis

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Allergy

Cite this

The novel cytokine interleukin-36α is expressed in psoriatic and rheumatoid arthritis synovium. / Frey, Silke; Derer, Anja; Messbacher, Maria Elena; Baeten, Dominique L P; Bugatti, Serena; Montecucco, Carlomaurizio; Schett, Georg; Hueber, Axel J.

In: Annals of the Rheumatic Diseases, Vol. 72, No. 9, 09.2013, p. 1569-1574.

Research output: Contribution to journalArticle

Frey, Silke ; Derer, Anja ; Messbacher, Maria Elena ; Baeten, Dominique L P ; Bugatti, Serena ; Montecucco, Carlomaurizio ; Schett, Georg ; Hueber, Axel J. / The novel cytokine interleukin-36α is expressed in psoriatic and rheumatoid arthritis synovium. In: Annals of the Rheumatic Diseases. 2013 ; Vol. 72, No. 9. pp. 1569-1574.
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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.",
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T1 - The novel cytokine interleukin-36α is expressed in psoriatic and rheumatoid arthritis synovium

AU - Frey, Silke

AU - Derer, Anja

AU - Messbacher, Maria Elena

AU - Baeten, Dominique L P

AU - Bugatti, Serena

AU - Montecucco, Carlomaurizio

AU - Schett, Georg

AU - Hueber, Axel J.

PY - 2013/9

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N2 - 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.

AB - 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.

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