Departments of Otolaryngology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Laboratory of Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan.
J Med Invest. 2020;67(3.4):311-314. doi: 10.2152/jmi.67.311.
The purpose of this study is to examine the effect of intranasal corticosteroid (INCS) administration on histamine H1 receptor (H1R) gene expression in the nasal mucosa of healthy participants and the effects of dexamethasone on basal and histamine-induced H1R mRNA expression, and histamine-induced phosphorylation of extracellular signal-regulated kinase (ERK) in HeLa cells. Sixteen healthy participants were given INCS once daily for a week. After pretreatment of dexamethasone, HeLa cells were treated with histamine. Levels of H1R mRNA and phosphorylation of ERK were measured using real time PCR and immunoblot analysis, respectively. Levels of H1R mRNA in the nasal mucosa of healthy participants receiving INCS was significantly decreased. Dexamethasone suppressed basal levels of H1R mRNA, and histamine-induced up-regulation of H1R mRNA and ERK phosphorylation in HeLa cells. These data suggested that corticosteroid inhibited both basal transcription and histamine-induced transcriptional activation of H1R through its suppression of ERK phosphorylation in the signaling pathway involved in H1R gene transcription. It is further suggested that pre-seasonal prophylactic administration of INCS suppresses both basal and pollen-induced upregulation of H1R gene expression in the nasal mucosa of patients with pollinosis, leading to prevention of the exacerbation of nasal symptoms during peak pollen season. J. Med. Invest. 67 : 311-314, August, 2020.
本研究旨在探讨鼻内皮质类固醇(INCS)给药对健康参与者鼻黏膜组织中组胺 H1 受体(H1R)基因表达的影响,以及地塞米松对 H1R mRNA 表达的基础水平和组胺诱导的表达、组胺诱导的细胞外信号调节激酶(ERK)磷酸化的影响。16 名健康参与者每日接受 INCS 治疗一周。地塞米松预处理后,用组胺处理 HeLa 细胞。使用实时 PCR 和免疫印迹分析分别测量 H1R mRNA 水平和 ERK 磷酸化水平。接受 INCS 治疗的健康参与者鼻黏膜中的 H1R mRNA 水平显著降低。地塞米松抑制 H1R mRNA 的基础水平,以及组胺诱导的 HeLa 细胞中 H1R mRNA 和 ERK 磷酸化的上调。这些数据表明,皮质类固醇通过抑制参与 H1R 基因转录的信号通路中的 ERK 磷酸化,抑制 H1R 的基础转录和组胺诱导的转录激活。进一步表明,在花粉症患者的鼻黏膜中,季节性预防性给予 INCS 可抑制 H1R 基因表达的基础水平和花粉诱导的上调,从而预防花粉高峰期鼻症状的恶化。医学研究杂志 67:311-314,2020 年 8 月。