NDLI: Macrolides Inhibit Fusobacterium nucleatum-Induced MUC5AC Production in Human Airway Epithelial Cells

Content Provider	PubMed Central
Author	Nagaoka, Kentaro Yanagihara, Katsunori Harada, Yosuke Yamada, Koichi Migiyama, Yohei Morinaga, Yoshitomo Hasegawa, Hiroo Izumikawa, Koichi Hiroshi, Kakeya Nishimura, Masaharu Shigeru, Kohno
Copyright Year	2013
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.
Related Links	http://dx.doi.org/10.1128/AAC.02466-12
Ending Page	1849
Page Count	6
Starting Page	1844
File Format	PDF
ISSN	10986596
e-ISSN	10986596
Journal	Antimicrobial Agents and Chemotherapy
Issue Number	4
Volume Number	57
Language	English
Publisher	American Society for Microbiology
Publisher Date	2013-04-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Pharmacology Pharmacology (medical)

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