Institute of Clinical Science, Zhongshan Hospital, Fudan University, Shanghai, China.
Respiratory Division of Zhongshan Hospital, Shanghai Institute of Respiratory Disease, Fudan University, Shanghai, China.
Mediators Inflamm. 2022 Oct 29;2022:1267841. doi: 10.1155/2022/1267841. eCollection 2022.
The current asthma therapies are inadequate for many patients with severe asthma. Pyrroloquinoline quinone (PQQ) is a naturally-occurring redox cofactor and nutrient that can exert a multitude of physiological effects, including anti-inflammatory and antioxidative effects. We sought to explore the effects of PQQ on allergic airway inflammation and reveal the underlying mechanisms. , the effects of PQQ on the secretion of epithelial-derived cytokines by house dust mite- (HDM-) incubated 16-HBE cells and on the differentiation potential of CD4+ T cells were investigated. , PQQ was administered to mice with ovalbumin- (OVA-) induced asthma, and lung pathology and inflammatory cell infiltration were assessed. The changes in T cell subsets and signal transducers and activators of transcription (STATs) were evaluated by flow cytometry. Pretreatment with PQQ significantly decreased HDM-stimulated thymic stromal lymphopoietin (TSLP) production in a dose-dependent manner in 16-HBE cells and inhibited Th2 cell differentiation . Treatment with PQQ significantly reduced bronchoalveolar lavage fluid (BALF) inflammatory cell counts in the OVA-induced mouse model. PQQ administration also changed the secretion of IFN- and IL-4 as well as the percentages of Th1, Th2, Th17, and Treg cells in the peripheral blood and lung tissues, along with inhibition the phosphorylation of STAT1, STAT3, and STAT6 while promoting that of STAT4 in allergic airway inflammation model mice. PQQ can alleviate allergic airway inflammation in mice by improving the immune microenvironment and regulating the JAK-STAT signaling pathway. Our findings suggest that PQQ has great potential as a novel therapeutic agent for inflammatory diseases, including asthma.
目前的哮喘疗法对许多重症哮喘患者来说并不足够。吡咯喹啉醌 (PQQ) 是一种天然存在的氧化还原辅助因子和营养素，可发挥多种生理作用，包括抗炎和抗氧化作用。我们试图探讨 PQQ 对过敏性气道炎症的影响，并揭示其潜在机制。在此，我们研究了 PQQ 对屋尘螨 (HDM-)孵育的 16-HBE 细胞上皮源性细胞因子分泌的影响以及对 CD4+T 细胞分化潜能的影响。然后，将 PQQ 给予卵清蛋白 (OVA)-诱导的哮喘小鼠，并评估肺病理学和炎症细胞浸润。通过流式细胞术评估 T 细胞亚群和信号转导子和转录激活子 (STAT) 的变化。PQQ 的预处理以剂量依赖性方式显著降低了 16-HBE 细胞中 HDM 刺激的胸腺基质淋巴细胞生成素 (TSLP) 的产生，并抑制了 Th2 细胞分化。PQQ 治疗显著降低了 OVA 诱导的小鼠模型中的支气管肺泡灌洗液 (BALF) 炎症细胞计数。PQQ 给药还改变了外周血和肺组织中 IFN-和 IL-4 的分泌以及 Th1、Th2、Th17 和 Treg 细胞的百分比，同时抑制了 STAT1、STAT3 和 STAT6 的磷酸化，而促进了过敏性气道炎症模型小鼠中 STAT4 的磷酸化。PQQ 可通过改善免疫微环境和调节 JAK-STAT 信号通路来减轻小鼠的过敏性气道炎症。我们的研究结果表明，PQQ 作为一种新型治疗炎症性疾病（包括哮喘）的药物具有很大的潜力。
