Takeda Kazuaki, Kaku Norihito, Morinaga Yoshitomo, Kosai Kosuke, Uno Naoki, Imamura Yoshifumi, Hasegawa Hiroo, Miyazaki Taiga, Izumikawa Koichi, Mukae Hiroshi, Yanagihara Katsunori
Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan; Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
J Infect Chemother. 2017 Sep;23(9):598-603. doi: 10.1016/j.jiac.2017.04.015. Epub 2017 Jul 17.
The innate immune system plays an important role in early immunity against respiratory tract infection. Although airway epithelial cells produce mucus to eliminate pathogens and irritants, hypersecretion of mucus is harmful for the host as it may cause airway obstruction and inhibit influx of antimicrobial agents. It has been reported that several antimicrobial agents have an immunomodulatory effect in vitro and in vivo, but little is known about whether tedizolid, a novel oxazolidinone, can modulate immune responses. In this study, we evaluated whether tedizolid can suppress MUC5AC production in human airway epithelial cells stimulated by methicillin-resistant Staphylococcus aureus (MRSA). Compared with the control, tedizolid significantly inhibited MUC5AC protein production and mRNA overexpression at concentrations of both 2 and 10 μg/mL (representative of trough and peak concentrations in human epithelial lining fluid). Among the mitogen-activated protein kinase inhibitors tested, only extracellular signal-regulated protein kinase 1/2 (ERK1/2) phosphorylation was inhibited by tedizolid as indicated by western blot analysis. These results indicate that tedizolid inhibits the overproduction of MUC5AC protein by inhibiting phosphorylation of ERK1/2. This study revealed that tedizolid suppresses excessive mucin production in human airway epithelial cells. The immunomodulatory effect of tedizolid may improve outcomes in patients with severe respiratory infectious diseases caused by MRSA.
先天性免疫系统在早期抵抗呼吸道感染的免疫过程中发挥着重要作用。尽管气道上皮细胞会产生黏液以清除病原体和刺激物，但黏液分泌过多对宿主有害，因为它可能导致气道阻塞并抑制抗菌剂的流入。据报道，几种抗菌剂在体外和体内均具有免疫调节作用，但对于新型恶唑烷酮类药物泰地唑胺是否能够调节免疫反应却知之甚少。在本研究中，我们评估了泰地唑胺是否能够抑制耐甲氧西林金黄色葡萄球菌（MRSA）刺激的人气道上皮细胞中MUC5AC的产生。与对照组相比，泰地唑胺在浓度为2和10μg/mL时（代表人体上皮衬液中的谷浓度和峰浓度）均能显著抑制MUC5AC蛋白的产生和mRNA的过表达。在测试的丝裂原活化蛋白激酶抑制剂中，蛋白质印迹分析表明，只有细胞外信号调节蛋白激酶1/2（ERK1/2）的磷酸化被泰地唑胺抑制。这些结果表明，泰地唑胺通过抑制ERK1/2的磷酸化来抑制MUC5AC蛋白的过量产生。本研究表明，泰地唑胺可抑制人气道上皮细胞中黏蛋白的过度产生。泰地唑胺的免疫调节作用可能会改善由MRSA引起的严重呼吸道感染疾病患者的预后。
