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.