The Novel Inducer of Innate Immunity HO53 Stimulates Autophagy in Human Airway Epithelial Cells
Aroylated phenylenediamines (APDs) are novel modulators of innate immunity with respect to enhancing the expression of antimicrobial peptides and maintaining epithelial barrier integrity. Here, we present a new study on induction of autophagy in human lung epithelial cells by the APD HO53. Interesti...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Karger Publishers
2022-01-01
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| Series: | Journal of Innate Immunity |
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| Online Access: | https://www.karger.com/Article/FullText/521602 |
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| author | Iwona T. Myszor Snaevar Sigurdsson Alexia Ros Viktorsdottir Birgitta Agerberth Eeva-Liisa Eskelinen Margret Helga Ogmundsdottir Gudmundur H. Gudmundsson |
| author_facet | Iwona T. Myszor Snaevar Sigurdsson Alexia Ros Viktorsdottir Birgitta Agerberth Eeva-Liisa Eskelinen Margret Helga Ogmundsdottir Gudmundur H. Gudmundsson |
| author_sort | Iwona T. Myszor |
| collection | DOAJ |
| description | Aroylated phenylenediamines (APDs) are novel modulators of innate immunity with respect to enhancing the expression of antimicrobial peptides and maintaining epithelial barrier integrity. Here, we present a new study on induction of autophagy in human lung epithelial cells by the APD HO53. Interestingly, HO53 affected autophagy in a dose-dependent manner, demonstrated by increased microtubule-associated proteins 1A/1B light-chain 3B (LC3B) processing in mature polarized bronchial epithelial cells. The quantification of LC3B puncta showed increased autophagy flux and formation of autophagosomes visualized by transmission electron microscopy. The phenotypic changes indicated that autophagy induction was associated with activation of 5′ adenosine monophosphate-activated protein kinase (AMPK), nuclear translocation of transcription factor EB (TFEB), and changes in expression of autophagy-related genes. The kinetics of the explored signaling pathways indicated on activation of AMPK followed by the nuclear translocation of TFEB. Moreover, our data suggest that HO53 modulates epigenetic changes related to induction of autophagy manifested by transcriptional regulation of histone-modifying enzymes. These changes were reflected by decreased ubiquitination of histone 2B at the lysine 120 residue that is associated with autophagy induction. Taken together, HO53 modulates autophagy, a part of the host defense system, through a complex mechanism involving several pathways and epigenetic events. |
| first_indexed | 2024-12-24T00:25:14Z |
| format | Article |
| id | doaj.art-9b0312b339784470bde7471b75cf1e7d |
| institution | Directory Open Access Journal |
| issn | 1662-811X 1662-8128 |
| language | English |
| last_indexed | 2024-12-24T00:25:14Z |
| publishDate | 2022-01-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Journal of Innate Immunity |
| spelling | doaj.art-9b0312b339784470bde7471b75cf1e7d2022-12-21T17:24:29ZengKarger PublishersJournal of Innate Immunity1662-811X1662-81282022-01-0111610.1159/000521602521602The Novel Inducer of Innate Immunity HO53 Stimulates Autophagy in Human Airway Epithelial CellsIwona T. Myszor0Snaevar Sigurdsson1https://orcid.org/0000-0003-4860-6311Alexia Ros Viktorsdottir2Birgitta Agerberth3Eeva-Liisa Eskelinen4https://orcid.org/0000-0003-0006-7785Margret Helga Ogmundsdottir5Gudmundur H. Gudmundsson6Department of Life and Environmental Sciences, Biomedical Center, University of Iceland, Reykjavik, IcelandDepartment of Life and Environmental Sciences, Biomedical Center, University of Iceland, Reykjavik, IcelandDepartment of Life and Environmental Sciences, Biomedical Center, University of Iceland, Reykjavik, IcelandDepartment of Laboratory Medicine, Clinical Microbiology, Karolinska Institutet, Huddinge, SwedenInstitute of Biomedicine, University of Turku, Turku, FinlandDepartment of Anatomy, Biomedical Center, Faculty of Medicine, University of Iceland, Reykjavik, IcelandDepartment of Life and Environmental Sciences, Biomedical Center, University of Iceland, Reykjavik, IcelandAroylated phenylenediamines (APDs) are novel modulators of innate immunity with respect to enhancing the expression of antimicrobial peptides and maintaining epithelial barrier integrity. Here, we present a new study on induction of autophagy in human lung epithelial cells by the APD HO53. Interestingly, HO53 affected autophagy in a dose-dependent manner, demonstrated by increased microtubule-associated proteins 1A/1B light-chain 3B (LC3B) processing in mature polarized bronchial epithelial cells. The quantification of LC3B puncta showed increased autophagy flux and formation of autophagosomes visualized by transmission electron microscopy. The phenotypic changes indicated that autophagy induction was associated with activation of 5′ adenosine monophosphate-activated protein kinase (AMPK), nuclear translocation of transcription factor EB (TFEB), and changes in expression of autophagy-related genes. The kinetics of the explored signaling pathways indicated on activation of AMPK followed by the nuclear translocation of TFEB. Moreover, our data suggest that HO53 modulates epigenetic changes related to induction of autophagy manifested by transcriptional regulation of histone-modifying enzymes. These changes were reflected by decreased ubiquitination of histone 2B at the lysine 120 residue that is associated with autophagy induction. Taken together, HO53 modulates autophagy, a part of the host defense system, through a complex mechanism involving several pathways and epigenetic events.https://www.karger.com/Article/FullText/521602bronchial epitheliumaroylated phenylenediamineadenosine monophosphate-activated protein kinasetranscription factor ebepigenetics |
| spellingShingle | Iwona T. Myszor Snaevar Sigurdsson Alexia Ros Viktorsdottir Birgitta Agerberth Eeva-Liisa Eskelinen Margret Helga Ogmundsdottir Gudmundur H. Gudmundsson The Novel Inducer of Innate Immunity HO53 Stimulates Autophagy in Human Airway Epithelial Cells Journal of Innate Immunity bronchial epithelium aroylated phenylenediamine adenosine monophosphate-activated protein kinase transcription factor eb epigenetics |
| title | The Novel Inducer of Innate Immunity HO53 Stimulates Autophagy in Human Airway Epithelial Cells |
| title_full | The Novel Inducer of Innate Immunity HO53 Stimulates Autophagy in Human Airway Epithelial Cells |
| title_fullStr | The Novel Inducer of Innate Immunity HO53 Stimulates Autophagy in Human Airway Epithelial Cells |
| title_full_unstemmed | The Novel Inducer of Innate Immunity HO53 Stimulates Autophagy in Human Airway Epithelial Cells |
| title_short | The Novel Inducer of Innate Immunity HO53 Stimulates Autophagy in Human Airway Epithelial Cells |
| title_sort | novel inducer of innate immunity ho53 stimulates autophagy in human airway epithelial cells |
| topic | bronchial epithelium aroylated phenylenediamine adenosine monophosphate-activated protein kinase transcription factor eb epigenetics |
| url | https://www.karger.com/Article/FullText/521602 |
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