Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Clin Exp Allergy. 2012 Feb;42(2):218-28. doi: 10.1111/j.1365-2222.2011.03867.x.
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.
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.
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.
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.
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.
白细胞介素 (IL)-33 是 IL-1 细胞因子家族的新成员，也是孤儿 IL-1 家族受体 ST2 的配体。IL-33 诱导辅助性 T 细胞 2 型炎症反应，被认为在过敏性炎症（如哮喘和特应性皮炎）中发挥关键作用。然而，IL-33 及其受体 ST2 在变应性鼻炎中的作用尚不清楚。
我们通过体外培养的正常人鼻上皮细胞（HNECs）研究了变应性鼻炎患者鼻上皮细胞中 IL-33 和 ST2 的表达，以及 IL-33 诱导细胞因子/趋化因子产生的机制。
采用逆转录聚合酶链反应和实时聚合酶链反应及免疫组化方法检测正常和变应性鼻炎鼻黏膜中 IL-33 和 ST2 的表达。采用 ELISA 法检测血清中 IL-33、IL-8 和 GM-CSF。进行体外实验时，采用原代培养的 HNECs。
变应性鼻炎患者血清中 IL-33 水平明显高于正常对照组。变应性鼻炎患者鼻上皮细胞中 IL-33 和 ST2 的表达明显升高。体外培养的 HNECs 经 IFN-γ和 Toll 样受体 9 配体 ODN2006 处理后，IL-33mRNA 表达明显增加。糖皮质激素治疗和 ERK、p38MAPK、JNK、NF-κB 和表皮生长因子受体的不同信号转导抑制剂可明显抑制 IL-33 诱导 HNECs 产生的 IL-8 和 GM-CSF。
IL-33 和其受体 ST2 在变应性鼻炎中发挥重要作用。在 HNECs 中，IL-33 通过 ST2 介导的炎症反应受不同信号通路的调节，IL-33/ST2 通路可能为变应性鼻炎提供新的治疗靶点。
