Azelastine enhances the clinical efficacy of glucocorticoid by modulating MKP-1 expression in allergic rhinitis
Azelastine enhances the clinical efficacy of glucocorticoid by modulating MKP-1 expression in allergic rhinitis
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氮卓斯汀通过调节变应性鼻炎中 MKP-1 的表达增强糖皮质激素的临床疗效
DOI：
10.1007/s00405-014-3191-3
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发表时间：
2015-05-01
影响因子：
2.6
通讯作者：
Li, Huabin
中科院分区：
文献类型：
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作者：
Luo, Xi;Ma, Renqiang;Li, Huabin
Azelastine建议作为糖皮质激素的补充选择，用于控制中重度变应性鼻炎（AR）。然而，其潜在的机制尚未被完全理解。本实验采用促炎因子（IL-1β和IL-17A）和抗炎剂（氮唑elastine和布地奈德）对体外培养的鼻上皮细胞和支气管上皮细胞进行刺激。分别采用qPCR和ELISA检测细胞间粘附分子1 （ICAM-1）和丝裂原活化蛋白激酶磷酸酶1 （MKP-1）的表达。此外，我们还对6例单独使用布地奈德鼻喷雾剂的未控制的严重AR患者进行了azelastine和布地奈德鼻喷雾剂对鼻腔ICAM-1水平和鼻腔总症状评分的叠加效应评估。我们发现azelastine显著抑制细胞因子诱导的ICAM-1上调，这种上调被MKP-1沉默逆转。Azelastine和budesonide可增加MKP-1的表达，抑制ICAM-1的表达。在连续治疗两周后，azelastine联合布地奈德鼻喷雾剂显著降低了6例未控制的AR患者鼻腔ICAM-1水平和TNSS。我们的研究结果表明，azelastine能够通过调节MKP-1的表达来增强布地奈德的抗炎作用，这可能与治疗不受控制的严重AR有关。
Azelastine was suggested as a supplementary choice of glucocorticoid for the control of moderate to severe allergic rhinitis (AR). However, the underlying mechanism has not been completely understood. In this study, primary cultured nasal epithelial cells and bronchial epithelial cells were stimulated with proinflammatory cytokines (IL-1β and IL-17A) and anti-inflammatory agents (azelastine and budesonide) in vitro. The expression of intercellular adhesion molecule 1 (ICAM-1) and mitogen-activated protein kinase phosphatase-1 (MKP-1) was examined using qPCR and ELISA, respectively. Moreover, the additive effects of azelastine and budesonide nasal spray on nasal ICAM-1 level and total nasal symptom scores were evaluated in six uncontrolled severe AR patients by budesonide nasal spray alone. We found azelastine significantly inhibited cytokine-induced ICAM-1 upregulation, which is reversed by MKP-1 silencing. Azelastine and budesonide additively increased MKP-1 expression and inhibited ICAM-1 expression in vitro. After treatment for two consecutive weeks, combined azelastine and budesonide nasal spray significantly decreased nasal ICAM-1 level and TNSS in six uncontrolled AR patients. Our findings suggested that azelastine is able to additively enhance the anti-inflammatory effect of budesonide by modulating MKP-1 expression, which may implicate in the treatment of uncontrolled severe AR.