title: The role of IL-33 and its receptor ST2 in human nasal epithelium with  allergic rhinitis.
abstract: BACKGROUND
  Interleukin (IL)-33 is a novel member of the IL-1 cytokine family and a ligand for the orphan IL-1 family receptor ST2. The IL-33 induces T helper 2-type inflammatory responses and is considered to play a crucial rule in allergic inflammations, such as asthma and atopic dermatitis. However, the role of IL-33 and its receptor ST2 in allergic rhinitis remains unknown.
  
  
  OBJECTIVE
  We investigated expression of IL-33 and ST2 in the nasal epithelium of patients with allergic rhinitis and the mechanisms of the production of cytokines/chemokines induced by treatment with IL-33 using normal human nasal epithelial cells (HNECs) in vitro.
  
  
  METHODS
  Expression of IL-33 and ST2 in normal and allergic rhinitis nasal mucosa was evaluated by reverse transcription- and real-time polymerase chain reactions and immunohistochemical methods. The IL-33 in serum, and IL-8 and GM-CSF were measured by ELISA. For in vitro experiments, HNECs in primary culture were used.
  
  
  RESULTS
  The IL-33 levels in the sera of patients with allergic rhinitis were significantly higher than that in normal controls. Expression of IL-33 and ST2 was significantly elevated in the epithelium from patients with allergic rhinitis. The IL-33 mRNA in HNECs in vitro was significantly induced by treatment with IFN-γ and the toll-like receptor 9 ligand ODN2006. The IL-33-induced production of IL-8 and GM-CSF from HNECs in vitro was significantly suppressed by corticosteroid treatment and distinct signal transduction inhibitors of ERK, p38 MAPK, JNK, NF-κB and epidermal growth factor receptor.
  
  
  CONCLUSIONS
  The IL-33 and its receptor ST2 play important roles in allergic rhinitis. The IL-33-mediated inflammatory responses via ST2 are regulated by distinct signalling pathways in HNECs and the IL-33/ST2 pathway may provide new therapeutic targets for allergic rhinitis.
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Kamekura
authors.forename: T
authors.initials: T
authors.lastname: Kojima
authors.forename: K
authors.initials: K
authors.lastname: Takano
authors.forename: M
authors.initials: M
authors.lastname: Go
authors.forename: N
authors.initials: N
authors.lastname: Sawada
authors.forename: T
authors.initials: T
authors.lastname: Himi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood / Q000235:genetics / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D016209:Interleukin-8 / Q000097:blood / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009297:Nasal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006255:Rhinitis, Allergic, Seasonal / Q000097:blood* / Q000235:genetics / Q000473:pathology; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; C508606:CXCL8 protein, human; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D016209:Interleukin-8; D007378:Interleukins; D016328:NF-kappa B; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C512478:EGFR protein, human; D066246:ErbB Receptors; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4