title: Blockade of IL-36 receptor signaling does not prevent from TNF-induced arthritis.
abstract: BACKGROUND
  Interleukin (IL)-36α is a newly described member of the IL-1 cytokine family with a known inflammatory and pathogenic function in psoriasis. Recently, we could demonstrate that the receptor (IL-36R), its ligand IL-36α and its antagonist IL-36Ra are expressed in synovial tissue of arthritis patients. Furthermore, IL-36α induces MAP-kinase and NFκB signaling in human synovial fibroblasts with subsequent expression and secretion of pro-inflammatory cytokines.
  
  
  METHODS
  To understand the pathomechanism of IL-36 dependent inflammation, we investigated the biological impact of IL-36α signaling in the hTNFtg mouse. Also the impact on osteoclastogenesis by IL-36α was tested in murine and human osteoclast assays.
  
  
  RESULTS
  Diseased mice showed an increased expression of IL-36R and IL-36α in inflamed knee joints compared to wildtype controls. However, preventively treating mice with an IL-36R blocking antibody led to no changes in clinical onset and pattern of disease. Furthermore, blockade of IL-36 signaling did not change histological signs of TNF-induced arthritis. Additionally, no alteration on bone homeostasis was observed in ex vivo murine and human osteoclast differentiation assays.
  
  
  CONCLUSIONS
  Thus we conclude that IL-36α does not affect the development of inflammatory arthritis.
authors.affiliation: Department of Internal Medicine 3 and Institute for Clinical Immunology, University Hospital Erlangen, Erlangen, Germany; Department of Radiation Oncology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Derer
authors.affiliation: Department of Internal Medicine 3 and Institute for Clinical Immunology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Groetsch
authors.affiliation: Department of Internal Medicine 3 and Institute for Clinical Immunology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Harre
authors.affiliation: Department of Internal Medicine 3 and Institute for Clinical Immunology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Böhm
authors.affiliation: Department of Inflammation Research, Amgen Inc., Longmont, Colorado, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Towne
authors.affiliation: Department of Internal Medicine 3 and Institute for Clinical Immunology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.affiliation: Department of Internal Medicine 3 and Institute for Clinical Immunology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Frey
authors.affiliation: Department of Internal Medicine 3 and Institute for Clinical Immunology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Axel J
authors.initials: AJ
authors.lastname: Hueber
mesh_terms: D000818:Animals; D001168:Arthritis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007719:Knee Joint / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D017472:Receptors, Interleukin-1 / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D007375:Interleukin-1; D017472:Receptors, Interleukin-1; C569500:Il1rl2 protein, mouse
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