| Summary: | Nagasaki University (長崎大学) 博士(医学) 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. 長崎大学学位論文 学位記番号:博(医歯薬)甲第1026号 学位授与年月日:平成30年3月7日 Author: Kazuaki Takeda, Norihito Kaku, Yoshitomo Morinaga, Kosuke Kosai, Naoki Uno, Yoshifumi Imamura, Hiroo Hasegawa, Taiga Miyazaki, Koichi Izumikawa, Hiroshi Mukae, Katsunori Yanagihara Citation: Journal of Infection and Chemotherapy, 23(9), pp.598-603; 2017 Nagasaki University (長崎大学), 博士(医学) (2018-03-07) doctoral thesis
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