Clarithromycin Modulates Neutrophilic Inflammation Induced by in Human Airway Epithelial Cells.

In the present study, we aimed to clarify the mechanisms by which periodontal pathogens, particularly , induce severe neutrophilic inflammation. In addition, we aimed to test the efficacy of macrolides, which has not been resolved in the neutrophilic inflammation induced by . NCl-H292 human airway epithelial cells were pre-incubated with clarithromycin for 2 h before incubation with supernatants. Then, C-X-C motif chemokine ligand 8 () transcription and interleukin (IL)-8 production were measured. To elucidate the signaling pathway, mitogen-activated protein kinase inhibitors were added to the cell culture, and the cells were subjected to Western blotting. supernatants promoted transcription and IL-8 production, and the reactions were significantly suppressed by clarithromycin pretreatment. Only trametinib, the selective mitogen-activated extracellular signal-regulated kinase inhibitor, downregulated transcription and IL-8 production. Furthermore, Western blotting revealed that stimulation with supernatants specifically induces extracellular signal-regulated kinases (ERK) 1/2 phosphorylation, which is suppressed by clarithromycin pretreatment. Notably, the interference analysis revealed that ERK3 might be dispensable for IL-8 production under the stimulation of supernatants. Our results provide new insight into the mechanism underlying -induced production of IL-8 from human airway epithelial cells. Furthermore, macrolides might have therapeutic potential in regulating periodontal pathogen-induced neutrophilic inflammation in the lungs.