Clarithromycin Modulates Neutrophilic Inflammation Induced by <i>Prevotella intermedia</i> in Human Airway Epithelial Cells

Clarithromycin Modulates Neutrophilic Inflammation Induced by <i>Prevotella intermedia</i> in Human Airway Epithelial Cells

<b>Objectives:</b> In the present study, we aimed to clarify the mechanisms by which periodontal pathogens, particularly <i>Prevotella intermedia</i>, induce severe neutrophilic inflammation. In addition, we aimed to test the efficacy of macrolides, which has not been resolve...

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Main Authors: Naoki Iwanaga, Ayaka Ota, Hiroki Ashizawa, Yuya Ito, Tatsuro Hirayama, Masataka Yoshida, Kazuaki Takeda, Shotaro Ide, Masato Tashiro, Naoki Hosogaya, Noriho Sakamoto, Takahiro Takazono, Kosuke Kosai, Mariko Naito, Yoshimasa Tanaka, Kazuhiro Yatera, Koichi Izumikawa, Katsunori Yanagihara, Hiroshi Mukae
Format: Article
Language:English
Published: MDPI AG 2024-09-01
Series:Antibiotics
Subjects:
<i>Prevotella intermedia</i>
clarithromycin
human airway epithelial cells
Online Access:https://www.mdpi.com/2079-6382/13/9/909
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Summary:<b>Objectives:</b> In the present study, we aimed to clarify the mechanisms by which periodontal pathogens, particularly <i>Prevotella intermedia</i>, 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 <i>P. intermedia</i>. <b>Methods:</b> NCl-H292 human airway epithelial cells were pre-incubated with clarithromycin for 2 h before incubation with <i>P. intermedia</i> supernatants. Then, C-X-C motif chemokine ligand 8 (<i>CXCL8</i>) 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. <b>Results:</b><i>P. intermedia</i> supernatants promoted <i>CXCL8</i> 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 <i>CXCL8</i> transcription and IL-8 production. Furthermore, Western blotting revealed that stimulation with <i>P. intermedia</i> 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 <i>P. intermedia</i> supernatants. <b>Conclusions:</b> Our results provide new insight into the mechanism underlying <i>P. intermedia</i>-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.
ISSN:2079-6382

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