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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2024-09-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Naoki Iwanaga |
| collection | DOAJ |
| description | <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. |
| format | Article |
| id | doaj-art-a3b2725af27243d4a7def22c9111aa13 |
| institution | OA Journals |
| issn | 2079-6382 |
| language | English |
| publishDate | 2024-09-01 |
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| series | Antibiotics |
| spelling | doaj-art-a3b2725af27243d4a7def22c9111aa132025-08-20T01:55:57ZengMDPI AGAntibiotics2079-63822024-09-0113990910.3390/antibiotics13090909Clarithromycin Modulates Neutrophilic Inflammation Induced by <i>Prevotella intermedia</i> in Human Airway Epithelial CellsNaoki Iwanaga0Ayaka Ota1Hiroki Ashizawa2Yuya Ito3Tatsuro Hirayama4Masataka Yoshida5Kazuaki Takeda6Shotaro Ide7Masato Tashiro8Naoki Hosogaya9Noriho Sakamoto10Takahiro Takazono11Kosuke Kosai12Mariko Naito13Yoshimasa Tanaka14Kazuhiro Yatera15Koichi Izumikawa16Katsunori Yanagihara17Hiroshi Mukae18Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki 852-8501, JapanDepartment of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, JapanDepartment of Respiratory Medicine, Nagasaki University Hospital, Nagasaki 852-8501, JapanDepartment of Respiratory Medicine, Nagasaki University Hospital, Nagasaki 852-8501, JapanDepartment of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, JapanDepartment of Respiratory Medicine, Nagasaki University Hospital, Nagasaki 852-8501, JapanDepartment of Respiratory Medicine, Nagasaki University Hospital, Nagasaki 852-8501, JapanDepartment of Infectious Diseases Experts Training Center, Nagasaki University Hospital, Nagasaki 852-8501, JapanDepartment of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, JapanDepartment of Respiratory Medicine, Nagasaki University Hospital, Nagasaki 852-8501, JapanDepartment of Respiratory Medicine, Nagasaki University Hospital, Nagasaki 852-8501, JapanDepartment of Respiratory Medicine, Nagasaki University Hospital, Nagasaki 852-8501, JapanDepartment of Laboratory Medicine, Nagasaki University Hospital, Nagasaki 852-8501, JapanDepartment of Microbiology and Oral Infection, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, JapanCenter for Medical Innovation, Nagasaki University, Nagasaki 852-8588, JapanDepartment of Respiratory Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, JapanDepartment of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, JapanDepartment of Laboratory Medicine, Nagasaki University Hospital, Nagasaki 852-8501, JapanDepartment of Respiratory Medicine, Nagasaki University Hospital, Nagasaki 852-8501, Japan<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.https://www.mdpi.com/2079-6382/13/9/909<i>Prevotella intermedia</i>clarithromycinhuman airway epithelial cells |
| spellingShingle | 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 Clarithromycin Modulates Neutrophilic Inflammation Induced by <i>Prevotella intermedia</i> in Human Airway Epithelial Cells Antibiotics <i>Prevotella intermedia</i> clarithromycin human airway epithelial cells |
| title | Clarithromycin Modulates Neutrophilic Inflammation Induced by <i>Prevotella intermedia</i> in Human Airway Epithelial Cells |
| title_full | Clarithromycin Modulates Neutrophilic Inflammation Induced by <i>Prevotella intermedia</i> in Human Airway Epithelial Cells |
| title_fullStr | Clarithromycin Modulates Neutrophilic Inflammation Induced by <i>Prevotella intermedia</i> in Human Airway Epithelial Cells |
| title_full_unstemmed | Clarithromycin Modulates Neutrophilic Inflammation Induced by <i>Prevotella intermedia</i> in Human Airway Epithelial Cells |
| title_short | Clarithromycin Modulates Neutrophilic Inflammation Induced by <i>Prevotella intermedia</i> in Human Airway Epithelial Cells |
| title_sort | clarithromycin modulates neutrophilic inflammation induced by i prevotella intermedia i in human airway epithelial cells |
| topic | <i>Prevotella intermedia</i> clarithromycin human airway epithelial cells |
| url | https://www.mdpi.com/2079-6382/13/9/909 |
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