title: Azithromycin inhibits MUC5AC induction via multidrug-resistant Acinetobacter baumannii in human airway epithelial cells.
abstract: 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.
authors.affiliation: 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.
authors.forename: Koichi
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Morinaga
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. Electronic address: k-yanagi@nagasaki-u.ac.jp.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Yanagihara
authors.affiliation: 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.
authors.forename: Norihito
authors.initials: N
authors.lastname: Kaku
authors.affiliation: 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.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Harada
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Uno
authors.affiliation: Second Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University Hospital, Nagasaki, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Second Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University Hospital, Nagasaki, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Imamura
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Hasegawa
authors.affiliation: Second Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University Hospital, Nagasaki, Japan.
authors.forename: Taiga
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: Second Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University Hospital, Nagasaki, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Izumikawa
authors.affiliation: Second Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University Hospital, Nagasaki, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kakeya
authors.affiliation: Department of Infection Control and Prevention, Aichi Medical University Graduate School of Medicine, Aichi, Japan.
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Mikamo
authors.affiliation: Second Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University Hospital, Nagasaki, Japan; Global COE Program, Nagasaki University, Nagasaki, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017963:Azithromycin / Q000494:pharmacology*; D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000382:microbiology; D002478:Cells, Cultured; D017291:Clarithromycin / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000382:microbiology; D005786:Gene Expression Regulation; D006801:Humans; D055271:Mucin 5AC / Q000378:metabolism*; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy / Q000382:microbiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000900:Anti-Bacterial Agents; D055271:Mucin 5AC; D017963:Azithromycin; D017291:Clarithromycin
keywords: Azithromycin; MUC5AC; Multidrug-resistant Acinetobacter baumannii; Ventilator-associated pneumonia