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IFN-γ-STAT1-ERK Pathway Mediates Protective Effects of Invariant Natural Killer T Cells Against Doxorubicin-Induced Cardiomyocyte Death
Doxorubicin (DOX)-induced cardiomyopathy has poor prognosis, and myocardial inflammation is intimately involved in its pathophysiology. The role of invariant natural killer T (iNKT) cells has not been fully determined in this disease. We here demonstrated that activation of iNKT cells by α-galactosy...
| Autores principales: | , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Elsevier
2023
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10504401/ https://www.ncbi.nlm.nih.gov/pubmed/37719427 http://dx.doi.org/10.1016/j.jacbts.2023.02.014 |
| _version_ | 1785106717476913152 |
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| author | Sada, Masashi Matsushima, Shouji Ikeda, Masataka Ikeda, Soichiro Okabe, Kosuke Ishikita, Akihito Tadokoro, Tomonori Enzan, Nobuyuki Yamamoto, Taishi Miyamoto, Hiroko Deguchi Tsutsui, Yoshitomo Miyake, Ryo Setoyama, Daiki Kang, Dongchon Ide, Tomomi Tsutsui, Hiroyuki |
| author_facet | Sada, Masashi Matsushima, Shouji Ikeda, Masataka Ikeda, Soichiro Okabe, Kosuke Ishikita, Akihito Tadokoro, Tomonori Enzan, Nobuyuki Yamamoto, Taishi Miyamoto, Hiroko Deguchi Tsutsui, Yoshitomo Miyake, Ryo Setoyama, Daiki Kang, Dongchon Ide, Tomomi Tsutsui, Hiroyuki |
| author_sort | Sada, Masashi |
| collection | PubMed |
| description | Doxorubicin (DOX)-induced cardiomyopathy has poor prognosis, and myocardial inflammation is intimately involved in its pathophysiology. The role of invariant natural killer T (iNKT) cells has not been fully determined in this disease. We here demonstrated that activation of iNKT cells by α-galactosylceramide (GC) attenuated DOX-induced cardiomyocyte death and cardiac dysfunction. αGC increased interferon (IFN)-γ and phosphorylation of signal transducers and activators of transcription 1 (STAT1) and extracellular signal-regulated kinase (ERK). Administration of anti-IFN-γ neutralizing antibody abrogated the beneficial effects of αGC on DOX-induced cardiac dysfunction. These findings emphasize the protective role of iNKT cells in DOX-induced cardiomyopathy via the IFN-γ-STAT1-ERK pathway. |
| format | Online Article Text |
| id | pubmed-10504401 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2023 |
| publisher | Elsevier |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-105044012023-09-17 IFN-γ-STAT1-ERK Pathway Mediates Protective Effects of Invariant Natural Killer T Cells Against Doxorubicin-Induced Cardiomyocyte Death Sada, Masashi Matsushima, Shouji Ikeda, Masataka Ikeda, Soichiro Okabe, Kosuke Ishikita, Akihito Tadokoro, Tomonori Enzan, Nobuyuki Yamamoto, Taishi Miyamoto, Hiroko Deguchi Tsutsui, Yoshitomo Miyake, Ryo Setoyama, Daiki Kang, Dongchon Ide, Tomomi Tsutsui, Hiroyuki JACC Basic Transl Sci Original Research - Preclinical Doxorubicin (DOX)-induced cardiomyopathy has poor prognosis, and myocardial inflammation is intimately involved in its pathophysiology. The role of invariant natural killer T (iNKT) cells has not been fully determined in this disease. We here demonstrated that activation of iNKT cells by α-galactosylceramide (GC) attenuated DOX-induced cardiomyocyte death and cardiac dysfunction. αGC increased interferon (IFN)-γ and phosphorylation of signal transducers and activators of transcription 1 (STAT1) and extracellular signal-regulated kinase (ERK). Administration of anti-IFN-γ neutralizing antibody abrogated the beneficial effects of αGC on DOX-induced cardiac dysfunction. These findings emphasize the protective role of iNKT cells in DOX-induced cardiomyopathy via the IFN-γ-STAT1-ERK pathway. Elsevier 2023-06-21 /pmc/articles/PMC10504401/ /pubmed/37719427 http://dx.doi.org/10.1016/j.jacbts.2023.02.014 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| spellingShingle | Original Research - Preclinical Sada, Masashi Matsushima, Shouji Ikeda, Masataka Ikeda, Soichiro Okabe, Kosuke Ishikita, Akihito Tadokoro, Tomonori Enzan, Nobuyuki Yamamoto, Taishi Miyamoto, Hiroko Deguchi Tsutsui, Yoshitomo Miyake, Ryo Setoyama, Daiki Kang, Dongchon Ide, Tomomi Tsutsui, Hiroyuki IFN-γ-STAT1-ERK Pathway Mediates Protective Effects of Invariant Natural Killer T Cells Against Doxorubicin-Induced Cardiomyocyte Death |
| title | IFN-γ-STAT1-ERK Pathway Mediates Protective Effects of Invariant Natural Killer T Cells Against Doxorubicin-Induced Cardiomyocyte Death |
| title_full | IFN-γ-STAT1-ERK Pathway Mediates Protective Effects of Invariant Natural Killer T Cells Against Doxorubicin-Induced Cardiomyocyte Death |
| title_fullStr | IFN-γ-STAT1-ERK Pathway Mediates Protective Effects of Invariant Natural Killer T Cells Against Doxorubicin-Induced Cardiomyocyte Death |
| title_full_unstemmed | IFN-γ-STAT1-ERK Pathway Mediates Protective Effects of Invariant Natural Killer T Cells Against Doxorubicin-Induced Cardiomyocyte Death |
| title_short | IFN-γ-STAT1-ERK Pathway Mediates Protective Effects of Invariant Natural Killer T Cells Against Doxorubicin-Induced Cardiomyocyte Death |
| title_sort | ifn-γ-stat1-erk pathway mediates protective effects of invariant natural killer t cells against doxorubicin-induced cardiomyocyte death |
| topic | Original Research - Preclinical |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10504401/ https://www.ncbi.nlm.nih.gov/pubmed/37719427 http://dx.doi.org/10.1016/j.jacbts.2023.02.014 |
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