title: Macrolides inhibit Fusobacterium nucleatum-induced MUC5AC production in human airway epithelial cells.
abstract: Fusobacterium nucleatum is one of the most common anaerobic bacteria in periodontitis and is responsible for several extraoral infections, including respiratory tract diseases. In this study, we examined whether F. nucleatum induces mucin secretion in airway epithelial cells. We also examined the effects of macrolides on F. nucleatum-induced mucus production compared with the effects of other antibiotics that exert anti-anaerobic activities. The production of MUC5AC, the major core protein of mucin secreted from the airway surface epithelium, in bronchial epithelial cells after stimulation with culture supernatants (Sup) of F. nucleatum was analyzed by performing enzyme-linked immunosorbent assay and quantitative RT-PCR. The cell-signaling pathway of F. nucleatum Sup stimulation was also analyzed by Western blotting. For inhibition studies, cells were treated with azithromycin, clarithromycin, clindamycin (CLDM), and metronidazole (MTZ). The F. nucleatum Sup induced NCI-H292 cells to express MUC5AC at both the protein level and the mRNA level in both a time- and dose-dependent manner. Macrolides inhibited F. nucleatum Sup-induced MUC5AC production, while CLDM and MTZ were less effective. F. nucleatum Sup induced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), and this induction was suppressed by macrolides. F. nucleatum Sup-induced MUC5AC production was blocked by the ERK pathway inhibitor U0126. F. nucleatum is likely to contribute to excessive mucin production, which suggests that periodontitis may correlate with the pathogenesis of chronic respiratory tract infection. Macrolides seem to reduce this mucin production and might represent an additional means of therapeutic intervention for F. nucleatum respiratory tract infections other than CLDM and MTZ.
authors: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors: Kentaro
authors: K
authors: Nagaoka
authors: Katsunori
authors: K
authors: Yanagihara
authors: Yosuke
authors: Y
authors: Harada
authors: Koichi
authors: K
authors: Yamada
authors: Yohei
authors: Y
authors: Migiyama
authors: Yoshitomo
authors: Y
authors: Morinaga
authors: Hiroo
authors: H
authors: Hasegawa
authors: Koichi
authors: K
authors: Izumikawa
authors: Hiroshi
authors: H
authors: Kakeya
authors: Masaharu
authors: M
authors: Nishimura
authors: Shigeru
authors: S
authors: Kohno
mesh_terms: D017963:Azithromycin / Q000494:pharmacology; D002460:Cell Line; D017291:Clarithromycin / Q000494:pharmacology; D002981:Clindamycin / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D016967:Fusobacterium nucleatum / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D018942:Macrolides / Q000494:pharmacology*; D008795:Metronidazole / Q000494:pharmacology; D055271:Mucin 5AC / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018942:Macrolides; D055271:Mucin 5AC; D008795:Metronidazole; D002981:Clindamycin; D017963:Azithromycin; D017291:Clarithromycin
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