Allergy and Cancer Center, Otorhinolaryngology Hospital, First Affiliated Hospital of Yat-sen University, and Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China.
Am J Rhinol Allergy. 2012 Sep-Oct;26(5):359-64. doi: 10.2500/ajra.2012.26.3795.
Although Interleukin (IL)-17A has been suggested to play a role in corticosteroid hyporesponsiveness, whether IL-17A is able to affect the sensitivity of MUC5AC to intranasal corticosteroid treatment in patients with allergic rhinitis (AR) is unclear.
Twenty patients with moderate to severe AR were enrolled in this study and the expression of MUC5AC, IL-17A, and glucocorticoid receptor beta (GR beta) was detected using immunochemical staining and quantitative reverse transcription polymerase chain reaction (RT-PCR) before and after treatment with fluticasone propionate (FP) nasal spray for 4 weeks, respectively. In addition, the effects of FP on IL-13- and IL-17A-induced MUC5AC and GR beta were also evaluated in the primarily cultured human nasal epithelial cells (HNECs) in vitro.
The increased MUC5AC expression was associated with IL-17A levels in AR, and IL-17A was found to affect the inhibition of MUC5AC by corticosteroid treatment. Both IL-13 and IL-17A significantly promoted MUC5AC mRNA expression in HNECs, and FP treatment was able to significantly inhibit MUC5AC mRNA expression in HNECs induced by IL-13 but not for that induced by IL-17A. Also, IL-17A but not IL-13 promoted GR beta mRNA expression in HNECs, which was not affected by administration of corticosteroid.
Our results suggest that the sensitivity of MUC5AC to topical corticosteroid is negatively associated with IL-17A in AR patients. This might help us to gain more insight into the pathophysiology and the pharmacotherapeutic mechanisms on AR treatment.
尽管白细胞介素(IL)-17A 已被认为在皮质类固醇低反应性中起作用,但 IL-17A 是否能够影响变应性鼻炎(AR)患者中 MUC5AC 对鼻内皮质类固醇治疗的敏感性尚不清楚。
本研究共纳入 20 例中重度 AR 患者,分别在丙酸氟替卡松(FP)鼻喷雾剂治疗 4 周前后,采用免疫化学染色和定量逆转录聚合酶链反应(RT-PCR)检测 MUC5AC、IL-17A 和糖皮质激素受体β(GRβ)的表达。此外,还在体外原代培养的人鼻上皮细胞(HNECs)中评估了 FP 对 IL-13 和 IL-17A 诱导的 MUC5AC 和 GRβ的影响。
AR 中 MUC5AC 表达的增加与 IL-17A 水平相关,且 IL-17A 影响皮质类固醇治疗对 MUC5AC 的抑制作用。IL-13 和 IL-17A 均可显著促进 HNECs 中 MUC5AC mRNA 的表达,而 FP 治疗可显著抑制 IL-13 诱导的 HNECs 中 MUC5AC mRNA 的表达,但对 IL-17A 诱导的无影响。此外,IL-17A 而非 IL-13 可促进 HNECs 中 GRβ mRNA 的表达,而皮质类固醇的给药对此无影响。
我们的结果表明,AR 患者 MUC5AC 对局部皮质类固醇的敏感性与 IL-17A 呈负相关。这可能有助于我们更深入地了解 AR 治疗的病理生理学和药物治疗机制。