Lung diseases, including asthma, pose a serious global health issue. Loss of mitochondrial function and decreased mitochondrial biogenesis play pivotal roles in the initiation and progression of chronic lung diseases. Thus, maintaining mitochondrial function and homeostasis is an important treatment goal. Zafirlukast is a CysLTR1 antagonist that is widely used as an adjuvant treatment for asthma. In the present study, we investigated the effects of zafirlukast in vitro using human bronchial epithelial cells (BECs). We performed measurements of oxygen consumption and bioenergetics and found that zafirlukast increased mitochondrial respiration and biogenesis in human BECs as evidenced by increased mitochondrial mass and mtDNA/nDNA. Through real-time PCR and western blot analysis, we found that zafirlukast significantly increased the expression of PGC-1α, NRF1, and TFAM at both the mRNA and protein levels. Finally, we determined that these effects are mediated through CREB signaling and that inhibition of CREB with its specific inhibitor H89 abolished the effects of zafirlukast described above. Thus, zafirlukast might have potential in enhancing mitochondrial function by promoting mitochondrial biogenesis in human bronchial epithelial cells through upregulating the expression of PGC-1α and activating the CREB pathway.

包括哮喘在内的肺部疾病是一个严重的全球健康问题。线粒体功能丧失和线粒体生物合成减少在慢性肺病的发生和发展中起关键作用。因此，维持线粒体功能和体内平衡是一个重要的治疗目标。Zafirlukast 是一种 CysLTR1 拮抗剂，广泛用作哮喘的辅助治疗。在本研究中，我们使用人支气管上皮细胞 (BEC) 在体外研究了扎鲁司特的作用。我们对耗氧量和生物能量学进行了测量，发现扎鲁司特增加了人类 BEC 中的线粒体呼吸和生物发生，线粒体质量和 mtDNA/nDNA 增加就证明了这一点。通过实时 PCR 和蛋白质印迹分析，我们发现扎鲁司特在 mRNA 和蛋白质水平均显着增加了 PGC-1α、NRF1 和 TFAM 的表达。最后，我们确定这些作用是通过 CREB ​​信号传导介导的，并且用其特异性抑制剂 H89 抑制 CREB ​​消除了上述扎鲁司特的作用。因此，扎鲁司特可能通过上调 PGC-1α 的表达和激活 CREB ​​通路促进人支气管上皮细胞中的线粒体生物合成来增强线粒体功能。