Giuseppe
Emeritus
[Source: Antimicrobial Agents and Chemotherapy, full text: (LINK). Abstract, edited.]
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Macrolides inhibit Fusobacterium nucleatum-induced MUC5AC induction in human airway epithelial cells
Kentaro Nagaoka, MD a,b,d, Katsunori Yanagihara, MD, PhDa,b,*, Yosuke Harada, MDa,b, Koichi Yamada, MDa,b, Yohei Migiyama, MDa,b, Yoshitomo Morinaga, MD, PhDa,b, Hiroo Hasegawa, MD, PhDa, Koichi Izumikawa, MD, PhDb, Hiroshi Kakeya, MD, PhDb, Masaharu Nishimura, MD, PhDd and Shigeru Kohno, MD, PhDb,c
Author Affiliations: <SUP>a</SUP>Department of Laboratory Medicine <SUP>b</SUP>Second Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan <SUP>c</SUP>Global COE Program, Nagasaki University, Nagasaki, Japan <SUP>d</SUP>First Department of Internal Medicine, Hokkaido University Hospital, Hokkaido, Japan
ABSTRACT
Fusobacterium nucleatum (Fn) is one of the most common anaerobic bacteria in periodontitis and is responsible for several extra-oral infections including respiratory tract diseases. In this study, we examined whether Fn induces mucin secretion in airway epithelial cells. We also examined the effects of macrolides on the Fn-induced mucus production compared with other antibiotics that exert anti-anaerobic activities. MUC5AC production in bronchial epithelial cells after stimulation with culture supernatants (Sup) of Fn was analyzed by performing enzyme-linked immunosorbent assay and quantitative RT-PCR. The cell-signaling pathway of Fn Sup stimulation was also analyzed by performing Western blotting. For inhibition studies, cells were treated with azithromycin, clarithromycin, clindamycin (CLDM), and metronidazole (MTZ). The Fn Sup-induced NCI-H292 cells to express MUC5AC at both the protein levels and the mRNA level in both a time- and dose-dependent manner. Macrolides inhibited Fn Sup-induced MUC5AC production, while CLDM and MTZ were less effective. Fn Sup induced the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, and this induction was suppressed by macrolides. Fn Sup-induced MUC5AC production was blocked by the ERK pathway inhibitor U0126. Fn is likely to contribute to excessive mucin production, which suggest that periodontitis may correlate with the pathogenesis of chronic respiratory tract infection. The macrolides seem to reduce this mucin production and might represent an additional therapeutic intervention for Fn respiratory tract infections other than CLDM and MTZ.
FOOTNOTES
*<SUP></SUP>Corresponding author: Katsunori Yanagihara, Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. Tel: +81-95-819-7418; Fax: +81-95-819-7257, E-mail: k-yanagi@nagasaki-u.ac.jp
Copyright ? 2013, American Society for Microbiology. All Rights Reserved.
-Kentaro Nagaoka, MD a,b,d, Katsunori Yanagihara, MD, PhDa,b,*, Yosuke Harada, MDa,b, Koichi Yamada, MDa,b, Yohei Migiyama, MDa,b, Yoshitomo Morinaga, MD, PhDa,b, Hiroo Hasegawa, MD, PhDa, Koichi Izumikawa, MD, PhDb, Hiroshi Kakeya, MD, PhDb, Masaharu Nishimura, MD, PhDd and Shigeru Kohno, MD, PhDb,c
Author Affiliations: <SUP>a</SUP>Department of Laboratory Medicine <SUP>b</SUP>Second Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan <SUP>c</SUP>Global COE Program, Nagasaki University, Nagasaki, Japan <SUP>d</SUP>First Department of Internal Medicine, Hokkaido University Hospital, Hokkaido, Japan
ABSTRACT
Fusobacterium nucleatum (Fn) is one of the most common anaerobic bacteria in periodontitis and is responsible for several extra-oral infections including respiratory tract diseases. In this study, we examined whether Fn induces mucin secretion in airway epithelial cells. We also examined the effects of macrolides on the Fn-induced mucus production compared with other antibiotics that exert anti-anaerobic activities. MUC5AC production in bronchial epithelial cells after stimulation with culture supernatants (Sup) of Fn was analyzed by performing enzyme-linked immunosorbent assay and quantitative RT-PCR. The cell-signaling pathway of Fn Sup stimulation was also analyzed by performing Western blotting. For inhibition studies, cells were treated with azithromycin, clarithromycin, clindamycin (CLDM), and metronidazole (MTZ). The Fn Sup-induced NCI-H292 cells to express MUC5AC at both the protein levels and the mRNA level in both a time- and dose-dependent manner. Macrolides inhibited Fn Sup-induced MUC5AC production, while CLDM and MTZ were less effective. Fn Sup induced the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, and this induction was suppressed by macrolides. Fn Sup-induced MUC5AC production was blocked by the ERK pathway inhibitor U0126. Fn is likely to contribute to excessive mucin production, which suggest that periodontitis may correlate with the pathogenesis of chronic respiratory tract infection. The macrolides seem to reduce this mucin production and might represent an additional therapeutic intervention for Fn respiratory tract infections other than CLDM and MTZ.
FOOTNOTES
*<SUP></SUP>Corresponding author: Katsunori Yanagihara, Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. Tel: +81-95-819-7418; Fax: +81-95-819-7257, E-mail: k-yanagi@nagasaki-u.ac.jp
Copyright ? 2013, American Society for Microbiology. All Rights Reserved.
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