c-Myb Dominates TBK1-Mediated Endotoxin Tolerance in Kupffer Cells by Negatively Regulating DTX4
As a protective mechanism regulating excessive inflammation, endotoxin tolerance plays a vital role in regulating endotoxin shock. Kupffer cells are players in mediating endotoxin tolerance. Nonetheless, the regulatory mechanism regulating endotoxin tolerance is barely known. A nonclassical IKK kina...
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2023/5990156 |
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| author | Yi-Lin Wu Le-Han Pan Zhu-Jun Yi Wen-Feng Zhang Jian-Ping Gong |
| author_facet | Yi-Lin Wu Le-Han Pan Zhu-Jun Yi Wen-Feng Zhang Jian-Ping Gong |
| author_sort | Yi-Lin Wu |
| collection | DOAJ |
| description | As a protective mechanism regulating excessive inflammation, endotoxin tolerance plays a vital role in regulating endotoxin shock. Kupffer cells are players in mediating endotoxin tolerance. Nonetheless, the regulatory mechanism regulating endotoxin tolerance is barely known. A nonclassical IKK kinase called TRAF-associated NF-κB activator (TANK)-binding kinase 1 (TBK1) can regulate inflammation. Here, we found that TBK1 is required for endotoxin tolerance in Kupffer cells. TBK1 plays a dominant role in regulating endotoxin tolerance by negatively regulating the induction of p100 processing. Deltex E3 ubiquitin ligase 4 (DTX4), a negative regulator of TBK1, can promote TBK1 K48-mediated ubiquitination and indirectly regulate endotoxin tolerance in Kupffer cells. We demonstrate that the c-Myb transcription factor could negatively regulate DTX4. Overexpression of c-Myb can be used to reduce the ubiquitination of TBK1 by reducing DTX4 transcription and to boost the anti-inflammatory effect of endotoxin tolerance. Thus, this study reveals a novel theory of TBK1-mediated endotoxin tolerance in Kupffer cells. |
| format | Article |
| id | doaj-art-cb3631042dbf48649e24e938c04bddda |
| institution | DOAJ |
| issn | 2314-7156 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-cb3631042dbf48649e24e938c04bddda2025-08-20T03:04:47ZengWileyJournal of Immunology Research2314-71562023-01-01202310.1155/2023/5990156c-Myb Dominates TBK1-Mediated Endotoxin Tolerance in Kupffer Cells by Negatively Regulating DTX4Yi-Lin Wu0Le-Han Pan1Zhu-Jun Yi2Wen-Feng Zhang3Jian-Ping Gong4Department of Hepatobiliary SurgeryDepartment of Hepatobiliary SurgeryDepartment of Hepatobiliary SurgeryDepartment of Hepatobiliary SurgeryDepartment of Hepatobiliary SurgeryAs a protective mechanism regulating excessive inflammation, endotoxin tolerance plays a vital role in regulating endotoxin shock. Kupffer cells are players in mediating endotoxin tolerance. Nonetheless, the regulatory mechanism regulating endotoxin tolerance is barely known. A nonclassical IKK kinase called TRAF-associated NF-κB activator (TANK)-binding kinase 1 (TBK1) can regulate inflammation. Here, we found that TBK1 is required for endotoxin tolerance in Kupffer cells. TBK1 plays a dominant role in regulating endotoxin tolerance by negatively regulating the induction of p100 processing. Deltex E3 ubiquitin ligase 4 (DTX4), a negative regulator of TBK1, can promote TBK1 K48-mediated ubiquitination and indirectly regulate endotoxin tolerance in Kupffer cells. We demonstrate that the c-Myb transcription factor could negatively regulate DTX4. Overexpression of c-Myb can be used to reduce the ubiquitination of TBK1 by reducing DTX4 transcription and to boost the anti-inflammatory effect of endotoxin tolerance. Thus, this study reveals a novel theory of TBK1-mediated endotoxin tolerance in Kupffer cells.http://dx.doi.org/10.1155/2023/5990156 |
| spellingShingle | Yi-Lin Wu Le-Han Pan Zhu-Jun Yi Wen-Feng Zhang Jian-Ping Gong c-Myb Dominates TBK1-Mediated Endotoxin Tolerance in Kupffer Cells by Negatively Regulating DTX4 Journal of Immunology Research |
| title | c-Myb Dominates TBK1-Mediated Endotoxin Tolerance in Kupffer Cells by Negatively Regulating DTX4 |
| title_full | c-Myb Dominates TBK1-Mediated Endotoxin Tolerance in Kupffer Cells by Negatively Regulating DTX4 |
| title_fullStr | c-Myb Dominates TBK1-Mediated Endotoxin Tolerance in Kupffer Cells by Negatively Regulating DTX4 |
| title_full_unstemmed | c-Myb Dominates TBK1-Mediated Endotoxin Tolerance in Kupffer Cells by Negatively Regulating DTX4 |
| title_short | c-Myb Dominates TBK1-Mediated Endotoxin Tolerance in Kupffer Cells by Negatively Regulating DTX4 |
| title_sort | c myb dominates tbk1 mediated endotoxin tolerance in kupffer cells by negatively regulating dtx4 |
| url | http://dx.doi.org/10.1155/2023/5990156 |
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