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 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.