慢性阻塞性肺疾病(COPD)是一种呼吸道炎症性疾病。补骨脂素(PSO)是传统上用于治疗COPD的补肾方川配方中确定的主要药理成分,但其在COPD炎症中的疗效未见报道.在这项研究中,我们旨在阐明PSO在COPD中的抗炎潜力,并阐明其潜在机制,关注T淋巴细胞募集和趋化因子的调节,即干扰素-γ(CXCL9)诱导的单核因子,干扰素诱导蛋白10(CXCL10),和干扰素诱导型T细胞α化学引诱物(CXCL11)。体外,RAW264.7由干扰素(IFN)-γ+香烟烟雾提取物(CSE)刺激,并用PSO(2.5,5,10μM)处理,然后通过实时PCR和Westernblot分析趋化因子的水平和Janus激酶(JAK)/信号转导和转录激活因子1(STAT1)通路的激活。在体内,在第1、8、15和22天通过腹膜内注射CSE建立小鼠模型,然后用PSO(10mg/kg)治疗。我们的体外实验表明,PSO降低了CXCL9,CXCL10和CXCL11的水平,并降低了JAK2和STAT1的蛋白质磷酸化水平。此外,PSO有效改善CSE暴露小鼠的炎性浸润并降低CD8+T细胞的比例。此外,PSO降低支气管肺泡灌洗液(BALF)和肺组织中CXCL9、CXCL10和CXCL11的水平,并降低JAK2和STAT1的蛋白磷酸化水平。总之,我们的结果揭示了PSO对COPD炎症的治疗潜力,可能通过JAK2/STAT1信号通路调节CD8+T细胞募集和趋化因子。
Chronic obstructive pulmonary disease (COPD) is a respiratory inflammatory disease. Psoralen (PSO) is the main pharmacological component identified from Bu-Shen-Fang-Chuan formula which has been traditionally used in treatment of COPD, yet its efficacy in COPD inflammation were unreported. In this study, we aimed to elucidate the anti-inflammatory potential of PSO in COPD and unravel the underlying mechanisms, focusing on T lymphocyte recruitment and the modulation of chemokines, namely monokine induced by interferon-gamma (CXCL9), interferon inducible protein 10 (CXCL10), and interferon inducible T-Cell alpha chemoattractant (CXCL11). In vitro, RAW264.7 was stimulated by interferon (IFN)-γ + cigarette smoke extract (CSE) and were treated with PSO (2.5, 5, 10 μM), then the levels of chemokines and the activation of Janus kinase (JAK)/Signal transducer and activator of transcription 1 (STAT1) pathway were analyzed by real time PCR and western blot. In vivo, a murine model was established by intraperitoneal injection of CSE on day 1, 8, 15, and 22, then treated with PSO (10 mg/kg). Our experiments in vitro illustrated that PSO reduced the levels of CXCL9, CXCL10, and CXCL11, and decreased the protein phosphorylation levels of JAK2 and STAT1. Additionally, PSO effectively improved inflammatory infiltration and decreased the proportion of CD8+ T cells in CSE-exposed mice. Furthermore, PSO reduced the levels of CXCL9, CXCL10, and CXCL11 in bronchoalveolar lavage fluid (BALF) and lung tissue, and decreased the protein phosphorylation levels of JAK2 and STAT1. In conclusion, our results revealed the therapeutic potential of PSO for COPD inflammation, possibly mediated through the regulation of CD8+ T cell recruitment and chemokines via the JAK2/STAT1 signaling pathway.