MEDIOGEN, Co., Ltd., Biovalley 1-ro, Jecheon-si 27159, Republic of Korea.
Molecules. 2022 Dec 21;28(1):61. doi: 10.3390/molecules28010061.
Airway epithelial cells are a major site of airway inflammation and may play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Diesel particulate matter (DPM) is associated with mucus hypersecretion and airway inflammation and has been reported to overexpress airway mucin in the NCI-H292 airway epithelial cells. Therefore, regulation of mucin hypersecretion is essential for developing novel anti-inflammatory agents. This study aimed to investigate the effects of cell-free supernatant (CFS) from and on nitro oxide (NO) production in RAW264.7 and proteins associated with mucus production in NCI-H292 cells. We observed that NO production was reduced by CFS from and in RAW 264.7, and , , and gene expression was increased by phosphorylation of nuclear factor kappa B (NF-κB) p65 and cAMP response element-binding protein (CREB) in DPM-stimulated NCI-H292 cells. However, CFS from MG4272, MG4577, MG4247, and MG5140 inhibited mRNA expression related to mucus production by downregulating the CREB/NfκB signaling pathway. These results suggest CFS from MG4272, MG4577, MG4247, and MG5140 can contribute as a strategic candidate to the prevention of airway inflammatory diseases caused by DPM.
气道上皮细胞是气道炎症的主要部位，可能在慢性阻塞性肺疾病（COPD）的发病机制中发挥重要作用。柴油颗粒物（DPM）与黏液过度分泌和气道炎症有关，并已报道在 NCI-H292 气道上皮细胞中过度表达气道黏蛋白。因此，调节黏蛋白过度分泌对于开发新型抗炎剂至关重要。本研究旨在研究 和 无细胞上清液（CFS）对 RAW264.7 中一氧化氮（NO）产生和 NCI-H292 细胞中与黏液产生相关的蛋白质的影响。我们观察到，来自 和 的 CFS 减少了 RAW264.7 中的 NO 产生，并且 DPM 刺激的 NCI-H292 细胞中 NF-κB p65 和 cAMP 反应元件结合蛋白（CREB）的磷酸化增加了 、 、 和 基因的表达。然而，来自 MG4272、MG4577、MG4247 和 MG5140 的 CFS 通过下调 CREB/NfκB 信号通路抑制与黏液产生相关的 mRNA 表达。这些结果表明，来自 MG4272、MG4577、MG4247 和 MG5140 的 CFS 可以作为预防由 DPM 引起的气道炎症性疾病的战略候选物。
