Bile acid metabolites enhance expression of cathelicidin antimicrobial peptide in airway epithelium through activation of the TGR5-ERK1/2 pathway
Abstract Signals for the maintenance of epithelial homeostasis are provided in part by commensal bacteria metabolites, that promote tissue homeostasis in the gut and remote organs as microbiota metabolites enter the bloodstream. In our study, we investigated the effects of bile acid metabolites, 3-o...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-57251-3 |
| _version_ | 1797247264878493696 |
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| author | Iwona T. Myszor Kornelia Lapka Kristjan Hermannsson Rokeya Sultana Rekha Peter Bergman Gudmundur Hrafn Gudmundsson |
| author_facet | Iwona T. Myszor Kornelia Lapka Kristjan Hermannsson Rokeya Sultana Rekha Peter Bergman Gudmundur Hrafn Gudmundsson |
| author_sort | Iwona T. Myszor |
| collection | DOAJ |
| description | Abstract Signals for the maintenance of epithelial homeostasis are provided in part by commensal bacteria metabolites, that promote tissue homeostasis in the gut and remote organs as microbiota metabolites enter the bloodstream. In our study, we investigated the effects of bile acid metabolites, 3-oxolithocholic acid (3-oxoLCA), alloisolithocholic acid (AILCA) and isolithocholic acid (ILCA) produced from lithocholic acid (LCA) by microbiota, on the regulation of innate immune responses connected to the expression of host defense peptide cathelicidin in lung epithelial cells. The bile acid metabolites enhanced expression of cathelicidin at low concentrations in human bronchial epithelial cell line BCi-NS1.1 and primary bronchial/tracheal cells (HBEpC), indicating physiological relevance for modulation of innate immunity in airway epithelium by bile acid metabolites. Our study concentrated on deciphering signaling pathways regulating expression of human cathelicidin, revealing that LCA and 3-oxoLCA activate the surface G protein-coupled bile acid receptor 1 (TGR5, Takeda-G-protein-receptor-5)—extracellular signal-regulated kinase (ERK1/2) cascade, rather than the nuclear receptors, aryl hydrocarbon receptor, farnesoid X receptor and vitamin D3 receptor in bronchial epithelium. Overall, our study provides new insights into the modulation of innate immune responses by microbiota bile acid metabolites in the gut-lung axis, highlighting the differences in epithelial responses between different tissues. |
| first_indexed | 2024-04-24T19:55:56Z |
| format | Article |
| id | doaj.art-55169c6bc48f451b9a6854148e80d563 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-24T19:55:56Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-55169c6bc48f451b9a6854148e80d5632024-03-24T12:19:55ZengNature PortfolioScientific Reports2045-23222024-03-0114111210.1038/s41598-024-57251-3Bile acid metabolites enhance expression of cathelicidin antimicrobial peptide in airway epithelium through activation of the TGR5-ERK1/2 pathwayIwona T. Myszor0Kornelia Lapka1Kristjan Hermannsson2Rokeya Sultana Rekha3Peter Bergman4Gudmundur Hrafn Gudmundsson5Faculty of Life and Environmental Sciences, Biomedical Center, University of IcelandFaculty of Life and Environmental Sciences, Biomedical Center, University of IcelandFaculty of Life and Environmental Sciences, Biomedical Center, University of IcelandDepartment of Laboratory Medicine, Karolinska InstitutetDepartment of Laboratory Medicine, Karolinska InstitutetFaculty of Life and Environmental Sciences, Biomedical Center, University of IcelandAbstract Signals for the maintenance of epithelial homeostasis are provided in part by commensal bacteria metabolites, that promote tissue homeostasis in the gut and remote organs as microbiota metabolites enter the bloodstream. In our study, we investigated the effects of bile acid metabolites, 3-oxolithocholic acid (3-oxoLCA), alloisolithocholic acid (AILCA) and isolithocholic acid (ILCA) produced from lithocholic acid (LCA) by microbiota, on the regulation of innate immune responses connected to the expression of host defense peptide cathelicidin in lung epithelial cells. The bile acid metabolites enhanced expression of cathelicidin at low concentrations in human bronchial epithelial cell line BCi-NS1.1 and primary bronchial/tracheal cells (HBEpC), indicating physiological relevance for modulation of innate immunity in airway epithelium by bile acid metabolites. Our study concentrated on deciphering signaling pathways regulating expression of human cathelicidin, revealing that LCA and 3-oxoLCA activate the surface G protein-coupled bile acid receptor 1 (TGR5, Takeda-G-protein-receptor-5)—extracellular signal-regulated kinase (ERK1/2) cascade, rather than the nuclear receptors, aryl hydrocarbon receptor, farnesoid X receptor and vitamin D3 receptor in bronchial epithelium. Overall, our study provides new insights into the modulation of innate immune responses by microbiota bile acid metabolites in the gut-lung axis, highlighting the differences in epithelial responses between different tissues.https://doi.org/10.1038/s41598-024-57251-3 |
| spellingShingle | Iwona T. Myszor Kornelia Lapka Kristjan Hermannsson Rokeya Sultana Rekha Peter Bergman Gudmundur Hrafn Gudmundsson Bile acid metabolites enhance expression of cathelicidin antimicrobial peptide in airway epithelium through activation of the TGR5-ERK1/2 pathway Scientific Reports |
| title | Bile acid metabolites enhance expression of cathelicidin antimicrobial peptide in airway epithelium through activation of the TGR5-ERK1/2 pathway |
| title_full | Bile acid metabolites enhance expression of cathelicidin antimicrobial peptide in airway epithelium through activation of the TGR5-ERK1/2 pathway |
| title_fullStr | Bile acid metabolites enhance expression of cathelicidin antimicrobial peptide in airway epithelium through activation of the TGR5-ERK1/2 pathway |
| title_full_unstemmed | Bile acid metabolites enhance expression of cathelicidin antimicrobial peptide in airway epithelium through activation of the TGR5-ERK1/2 pathway |
| title_short | Bile acid metabolites enhance expression of cathelicidin antimicrobial peptide in airway epithelium through activation of the TGR5-ERK1/2 pathway |
| title_sort | bile acid metabolites enhance expression of cathelicidin antimicrobial peptide in airway epithelium through activation of the tgr5 erk1 2 pathway |
| url | https://doi.org/10.1038/s41598-024-57251-3 |
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