Exercise Inhibits Doxorubicin-Induced Cardiotoxicity via Regulating B Cells
BACKGROUND: Doxorubicin is an effective chemotherapeutic agent, but its use is limited by acute and chronic cardiotoxicity. Exercise training has been shown to protect against doxorubicin-induced cardiotoxicity, but the involvement of immune cells remains unclear. This study aimed to investigate the role of exercise-derived B cells in protecting against doxorubicin-induced cardiotoxicity and to further determine whether B cell activation and antibody secretion play a role in this protection.
METHODS: Mice that were administered with doxorubicin (5 mg/kg per week, 20 mg/kg cumulative dose) received treadmill running exercise. The adoptive transfer of exercise-derived splenic B cells to μMT-/- (B cell-deficient) mice was performed to elucidate the mechanism of B cell regulation that mediated the effect of exercise.
RESULTS: Doxorubicin-administered mice that had undergone exercise training showed improved cardiac function, and low levels of cardiac apoptosis, atrophy, and fibrosis, and had reduced cardiac antibody deposition and proinflammatory responses. Similarly, B cell pharmacological and genetic depletion alleviated doxorubicin-induced cardiotoxicity, which phenocopied the protection of exercise. In vitro performed coculture experiments confirmed that exercise-derived B cells reduced cardiomyocyte apoptosis and fibroblast activation compared with control B cells. Importantly, the protective effect of exercise on B cells was confirmed by the adoptive transfer of splenic B cells from exercised donor mice to μMT-/- recipient mice. However, blockage of Fc gamma receptor IIB function using B cell transplants from exercised Fc gamma receptor IIB-/- mice abolished the protection of exercise-derived B cells against doxorubicin-induced cardiotoxicity. Mechanistically, we found that Fc gamma receptor IIB, an important B cell inhibitory receptor, responded to exercise and increased B cell activation threshold, which participated in exercise-induced protection against doxorubicin-induced cardiotoxicity.
CONCLUSIONS: Our results demonstrate that exercise training protects against doxorubicin-induced cardiotoxicity by upregulating Fc gamma receptor IIB expression in B cells, which plays an important anti-inflammatory role and participates in the protective effect of exercise against doxorubicin-induced cardiotoxicity.
| Errataetall: |
CommentIn: Circ Res. 2024 Mar;134(5):569-571. - PMID 38422182 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:134 |
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| Enthalten in: |
Circulation research - 134(2024), 5 vom: 11. März, Seite 550-568 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Jing [VerfasserIn] |
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| Links: |
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| Themen: |
80168379AG |
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| Anmerkungen: |
Date Completed 04.03.2024 Date Revised 14.03.2024 published: Print-Electronic CommentIn: Circ Res. 2024 Mar;134(5):569-571. - PMID 38422182 Citation Status MEDLINE |
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| doi: |
10.1161/CIRCRESAHA.123.323346 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368126285 |
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| 245 | 1 | 0 | |a Exercise Inhibits Doxorubicin-Induced Cardiotoxicity via Regulating B Cells |
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| 500 | |a CommentIn: Circ Res. 2024 Mar;134(5):569-571. - PMID 38422182 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Doxorubicin is an effective chemotherapeutic agent, but its use is limited by acute and chronic cardiotoxicity. Exercise training has been shown to protect against doxorubicin-induced cardiotoxicity, but the involvement of immune cells remains unclear. This study aimed to investigate the role of exercise-derived B cells in protecting against doxorubicin-induced cardiotoxicity and to further determine whether B cell activation and antibody secretion play a role in this protection | ||
| 520 | |a METHODS: Mice that were administered with doxorubicin (5 mg/kg per week, 20 mg/kg cumulative dose) received treadmill running exercise. The adoptive transfer of exercise-derived splenic B cells to μMT-/- (B cell-deficient) mice was performed to elucidate the mechanism of B cell regulation that mediated the effect of exercise | ||
| 520 | |a RESULTS: Doxorubicin-administered mice that had undergone exercise training showed improved cardiac function, and low levels of cardiac apoptosis, atrophy, and fibrosis, and had reduced cardiac antibody deposition and proinflammatory responses. Similarly, B cell pharmacological and genetic depletion alleviated doxorubicin-induced cardiotoxicity, which phenocopied the protection of exercise. In vitro performed coculture experiments confirmed that exercise-derived B cells reduced cardiomyocyte apoptosis and fibroblast activation compared with control B cells. Importantly, the protective effect of exercise on B cells was confirmed by the adoptive transfer of splenic B cells from exercised donor mice to μMT-/- recipient mice. However, blockage of Fc gamma receptor IIB function using B cell transplants from exercised Fc gamma receptor IIB-/- mice abolished the protection of exercise-derived B cells against doxorubicin-induced cardiotoxicity. Mechanistically, we found that Fc gamma receptor IIB, an important B cell inhibitory receptor, responded to exercise and increased B cell activation threshold, which participated in exercise-induced protection against doxorubicin-induced cardiotoxicity | ||
| 520 | |a CONCLUSIONS: Our results demonstrate that exercise training protects against doxorubicin-induced cardiotoxicity by upregulating Fc gamma receptor IIB expression in B cells, which plays an important anti-inflammatory role and participates in the protective effect of exercise against doxorubicin-induced cardiotoxicity | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a B cells | |
| 650 | 4 | |a FcγRIIB | |
| 650 | 4 | |a cardiotoxicity | |
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| 650 | 4 | |a exercise training | |
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| 700 | 1 | |a Meng, Xinxiu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Xuan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Tianhui |e verfasserin |4 aut | |
| 700 | 1 | |a Lei, Zhiyong |e verfasserin |4 aut | |
| 700 | 1 | |a Lehmann, H Immo |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Guoping |e verfasserin |4 aut | |
| 700 | 1 | |a Alcaide, Pilar |e verfasserin |4 aut | |
| 700 | 1 | |a Bei, Yihua |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Junjie |e verfasserin |4 aut | |
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