title: Interleukin-33 synergistically enhances immune complex-induced tumor necrosis factor alpha and interleukin-8 production in cultured human synovium-derived mast cells.
abstract: BACKGROUND
  Substantial evidence suggests that human synovial mast cells (MCs) are involved in the pathogenesis of rheumatoid arthritis (RA). Interleukin (IL)-33 is believed to play an important role in the pathogenesis of RA. We recently reported that FcγRI is responsible for producing abundant tumor necrosis factor alpha (TNF-α) from cultured synovium-derived MCs (SyMCs) in response to aggregated immunoglobulin G (IgG). However, whether or not IL-33 affects immune complex (IC)-induced synovial MC activation remains unknown. This study sought to evaluate the effect of IL-33 on IC-induced synovial MC activation.
  
  
  METHODS
  Cultured SyMCs were generated by culturing synovial cells with stem cell factor. ST2 expression was analyzed using FACS and immunohistochemical techniques. Mediators released from the MCs were measured using EIAs or ELISAs.
  
  
  RESULTS
  SyMCs obtained from patients with RA or osteoarthritis (OA) expressed ST2 on their surfaces. We confirmed the expression of ST2 in MCs using immunofluorescence staining in joint tissue obtained from RA patients. IC-triggered histamine release was not enhanced by IL-33. However, IL-33 synergistically enhanced IC-induced IL-8 and TNF-α production in SyMCs.
  
  
  CONCLUSIONS
  ICs and IL-33 may exacerbate inflammation associated with RA by abundantly producing TNF-α and IL-8 from SyMCs.
authors.affiliation: Department of Molecular Cell Immunology and Allergology, Nihon University School of Medicine, Tokyo, Japan. jkashiwakura@rcai.riken.jp
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kashiwakura
authors.forename: Masahiko
authors.initials: M
authors.lastname: Yanagisawa
authors.forename: Hyunho
authors.initials: H
authors.lastname: Lee
authors.forename: Yuki
authors.initials: Y
authors.lastname: Okamura
authors.forename: Tomomi
authors.initials: T
authors.lastname: Sasaki-Sakamoto
authors.forename: Shu
authors.initials: S
authors.lastname: Saito
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tokuhashi
authors.forename: Chisei
authors.initials: C
authors.lastname: Ra
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Okayama
mesh_terms: D000936:Antigen-Antibody Complex / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D016209:Interleukin-8 / Q000096:biosynthesis*; D007378:Interleukins / Q000494:pharmacology*; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D013583:Synovial Membrane / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D000936:Antigen-Antibody Complex; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D016209:Interleukin-8; D007378:Interleukins; D011956:Receptors, Cell Surface; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha