Oxidative stress induces MUC5AC expression through mitochondrial damage‐dependent STING signaling in human bronchial epithelial cells
Abstract Oxidative stress increases the production of the predominant mucin MUC5AC in airway epithelial cells and is implicated in the pathogenesis of bronchial asthma and chronic obstructive pulmonary disease. Oxidative stress impairs mitochondria, releasing mitochondrial DNA into the cytoplasm and...
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| Format: | Article |
| Language: | English |
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Wiley
2023-04-01
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| Series: | FASEB BioAdvances |
| Subjects: | |
| Online Access: | https://doi.org/10.1096/fba.2022-00081 |
| _version_ | 1797853390168915968 |
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| author | Yutaka Nishida Hisako Yagi Masaya Ota Atsushi Tanaka Koichiro Sato Takaharu Inoue Satoshi Yamada Naoya Arakawa Takashi Ishige Yasuko Kobayashi Hirokazu Arakawa Takumi Takizawa |
| author_facet | Yutaka Nishida Hisako Yagi Masaya Ota Atsushi Tanaka Koichiro Sato Takaharu Inoue Satoshi Yamada Naoya Arakawa Takashi Ishige Yasuko Kobayashi Hirokazu Arakawa Takumi Takizawa |
| author_sort | Yutaka Nishida |
| collection | DOAJ |
| description | Abstract Oxidative stress increases the production of the predominant mucin MUC5AC in airway epithelial cells and is implicated in the pathogenesis of bronchial asthma and chronic obstructive pulmonary disease. Oxidative stress impairs mitochondria, releasing mitochondrial DNA into the cytoplasm and inducing inflammation through the intracytoplasmic DNA sensor STING (stimulator of interferon genes). However, the role of innate immunity in mucin production remains unknown. We aimed to elucidate the role of innate immunity in mucin production in airway epithelial cells under oxidative stress. Human airway epithelial cell line (NCI‐H292) and normal human bronchial epithelial cells were used to confirm MUC5AC expression levels by real‐time PCR when stimulated with hydrogen peroxide (H2O2). MUC5AC transcriptional activity was increased and mitochondrial DNA was released into the cytosol by H2O2. Mitochondrial antioxidants were used to confirm the effects of mitochondrial oxidative stress where antioxidants inhibited the increase in MUC5AC transcriptional activity. Cyclic GMP‐AMP synthase (cGAS) or STING knockout (KO) cells were generated to investigate their involvement. H2O2‐induced MUC5AC expression was suppressed in STING KO cells, but not in cGAS KO cells. The epidermal growth factor receptor was comparably expressed in STING KO and wild‐type cells. Thus, mitochondria and STING play important roles in mucin production in response to oxidative stress in airway epithelial cells. |
| first_indexed | 2024-04-09T19:49:53Z |
| format | Article |
| id | doaj.art-7ce6d1dca47447949520730d86860bc3 |
| institution | Directory Open Access Journal |
| issn | 2573-9832 |
| language | English |
| last_indexed | 2024-04-09T19:49:53Z |
| publishDate | 2023-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | FASEB BioAdvances |
| spelling | doaj.art-7ce6d1dca47447949520730d86860bc32023-04-03T10:10:54ZengWileyFASEB BioAdvances2573-98322023-04-015417118110.1096/fba.2022-00081Oxidative stress induces MUC5AC expression through mitochondrial damage‐dependent STING signaling in human bronchial epithelial cellsYutaka Nishida0Hisako Yagi1Masaya Ota2Atsushi Tanaka3Koichiro Sato4Takaharu Inoue5Satoshi Yamada6Naoya Arakawa7Takashi Ishige8Yasuko Kobayashi9Hirokazu Arakawa10Takumi Takizawa11Department of Pediatrics Gunma University Graduate School of Medicine Gunma JapanDepartment of Pediatrics Gunma University Graduate School of Medicine Gunma JapanDepartment of Pediatrics Gunma University Graduate School of Medicine Gunma JapanDepartment of Medicine, Research Institute of Medical Sciences Yamagata University Yamagata JapanDepartment of Pediatrics Gunma University Graduate School of Medicine Gunma JapanDepartment of Pediatrics Gunma University Graduate School of Medicine Gunma JapanDepartment of Pediatrics Gunma University Graduate School of Medicine Gunma JapanDepartment of Pediatrics Gunma University Graduate School of Medicine Gunma JapanDepartment of Pediatrics Gunma University Graduate School of Medicine Gunma JapanDepartment of Pediatrics Gunma University Graduate School of Medicine Gunma JapanDepartment of Pediatrics Gunma University Graduate School of Medicine Gunma JapanDepartment of Pediatrics Gunma University Graduate School of Medicine Gunma JapanAbstract Oxidative stress increases the production of the predominant mucin MUC5AC in airway epithelial cells and is implicated in the pathogenesis of bronchial asthma and chronic obstructive pulmonary disease. Oxidative stress impairs mitochondria, releasing mitochondrial DNA into the cytoplasm and inducing inflammation through the intracytoplasmic DNA sensor STING (stimulator of interferon genes). However, the role of innate immunity in mucin production remains unknown. We aimed to elucidate the role of innate immunity in mucin production in airway epithelial cells under oxidative stress. Human airway epithelial cell line (NCI‐H292) and normal human bronchial epithelial cells were used to confirm MUC5AC expression levels by real‐time PCR when stimulated with hydrogen peroxide (H2O2). MUC5AC transcriptional activity was increased and mitochondrial DNA was released into the cytosol by H2O2. Mitochondrial antioxidants were used to confirm the effects of mitochondrial oxidative stress where antioxidants inhibited the increase in MUC5AC transcriptional activity. Cyclic GMP‐AMP synthase (cGAS) or STING knockout (KO) cells were generated to investigate their involvement. H2O2‐induced MUC5AC expression was suppressed in STING KO cells, but not in cGAS KO cells. The epidermal growth factor receptor was comparably expressed in STING KO and wild‐type cells. Thus, mitochondria and STING play important roles in mucin production in response to oxidative stress in airway epithelial cells.https://doi.org/10.1096/fba.2022-00081hydrogen peroxidemitochondriamtDNAMUC5ACoxidative stressSTING |
| spellingShingle | Yutaka Nishida Hisako Yagi Masaya Ota Atsushi Tanaka Koichiro Sato Takaharu Inoue Satoshi Yamada Naoya Arakawa Takashi Ishige Yasuko Kobayashi Hirokazu Arakawa Takumi Takizawa Oxidative stress induces MUC5AC expression through mitochondrial damage‐dependent STING signaling in human bronchial epithelial cells FASEB BioAdvances hydrogen peroxide mitochondria mtDNA MUC5AC oxidative stress STING |
| title | Oxidative stress induces MUC5AC expression through mitochondrial damage‐dependent STING signaling in human bronchial epithelial cells |
| title_full | Oxidative stress induces MUC5AC expression through mitochondrial damage‐dependent STING signaling in human bronchial epithelial cells |
| title_fullStr | Oxidative stress induces MUC5AC expression through mitochondrial damage‐dependent STING signaling in human bronchial epithelial cells |
| title_full_unstemmed | Oxidative stress induces MUC5AC expression through mitochondrial damage‐dependent STING signaling in human bronchial epithelial cells |
| title_short | Oxidative stress induces MUC5AC expression through mitochondrial damage‐dependent STING signaling in human bronchial epithelial cells |
| title_sort | oxidative stress induces muc5ac expression through mitochondrial damage dependent sting signaling in human bronchial epithelial cells |
| topic | hydrogen peroxide mitochondria mtDNA MUC5AC oxidative stress STING |
| url | https://doi.org/10.1096/fba.2022-00081 |
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