Yamada Koichi, Morinaga Yoshitomo, Yanagihara Katsunori, Kaku Norihito, Harada Yosuke, Uno Naoki, Nakamura Shigeki, Imamura Yoshifumi, Hasegawa Hiroo, Miyazaki Taiga, Izumikawa Koichi, Kakeya Hiroshi, Mikamo Hiroshige, Kohno Shigeru
Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan; Second Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University Hospital, Nagasaki, Japan.
Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Pulm Pharmacol Ther. 2014 Aug;28(2):165-70. doi: 10.1016/j.pupt.2014.05.006. Epub 2014 Jun 6.
Acinetobacter baumannii is one of the main pathogens that cause ventilator-associated pneumonia (VAP). Hypersecretion of mucin in the airway is associated with the onset of VAP. Furthermore, macrolides are known to accelerate the resolution of VAP. However, this mechanism has not been elucidated. We examined whether macrolides inhibit MUC5AC production that is induced by multidrug-resistant A. baumannii (MDRAB). MUC5AC production in bronchial cells after MDRAB stimulation was analyzed by enzyme-linked immunosorbent assay and quantitative reverse transcription-polymerase chain reaction. For the inhibition study, cells were treated with azithromycin (AZM) or clarithromycin (CAM) simultaneously along with MDRAB stimulation. Western blotting was performed was performed to determine potential rules for signal modules. MDRAB induced MUC5AC production and gene expression. The EGFR-ERK/JNK-NF-κB pathway was involved in MDRAB-induced MUC5AC production. AZM but not CAM inhibited MUC5AC production. AZM suppressed the phosphorylation of ERK/JNK and the nuclear translocation of NF-κB. Our results suggest that the efficacy of macrolides against VAP may be due to the inhibition of mucin production.
鲍曼不动杆菌是引起呼吸机相关性肺炎（VAP）的主要病原体之一。气道中粘蛋白的过度分泌与VAP的发病有关。此外，已知大环内酯类药物可加速VAP的消退。然而，这一机制尚未阐明。我们研究了大环内酯类药物是否抑制多重耐药鲍曼不动杆菌（MDRAB）诱导的MUC5AC产生。通过酶联免疫吸附测定和定量逆转录-聚合酶链反应分析MDRAB刺激后支气管细胞中MUC5AC的产生。为了进行抑制研究，在MDRAB刺激的同时，用阿奇霉素（AZM）或克拉霉素（CAM）处理细胞。进行蛋白质印迹以确定信号模块的潜在规则。MDRAB诱导MUC5AC产生和基因表达。EGFR-ERK/JNK-NF-κB途径参与MDRAB诱导的MUC5AC产生。AZM而非CAM抑制MUC5AC产生。AZM抑制ERK/JNK的磷酸化和NF-κB的核转位。我们的结果表明，大环内酯类药物对VAP的疗效可能归因于对粘蛋白产生的抑制。
