The role of IL-33 and its receptor ST2 in human nasal epithelium with allergic rhinitis

Clin Exp Allergy. 2012 Feb;42(2):218-28. doi: 10.1111/j.1365-2222.2011.03867.x.


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 and clinical relevance: 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / pharmacology
  • Cells, Cultured
  • ErbB Receptors / genetics
  • ErbB Receptors / immunology
  • ErbB Receptors / metabolism
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / blood
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukin-8 / blood
  • Interleukin-8 / genetics
  • Interleukin-8 / immunology
  • Interleukins / biosynthesis
  • Interleukins / genetics
  • Interleukins / immunology*
  • MAP Kinase Kinase 4 / genetics
  • MAP Kinase Kinase 4 / immunology
  • MAP Kinase Kinase 4 / metabolism
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / genetics
  • MAP Kinase Signaling System / immunology*
  • Male
  • Middle Aged
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • NF-kappa B / metabolism
  • Nasal Mucosa / immunology*
  • Nasal Mucosa / metabolism
  • Nasal Mucosa / pathology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Messenger / immunology
  • Real-Time Polymerase Chain Reaction
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology*
  • Receptors, Cell Surface / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rhinitis, Allergic, Seasonal / blood*
  • Rhinitis, Allergic, Seasonal / genetics
  • Rhinitis, Allergic, Seasonal / pathology
  • Toll-Like Receptor 9 / agonists
  • Toll-Like Receptor 9 / genetics
  • Toll-Like Receptor 9 / immunology
  • Toll-Like Receptor 9 / metabolism
  • Young Adult
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / immunology
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Antiviral Agents
  • CXCL8 protein, human
  • IL1RL1 protein, human
  • IL33 protein, human
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukin-8
  • Interleukins
  • NF-kappa B
  • RNA, Messenger
  • Receptors, Cell Surface
  • TLR9 protein, human
  • Toll-Like Receptor 9
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • EGFR protein, human
  • ErbB Receptors
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4