Interleukin-10 exhibit dose-dependent effects on macrophage phenotypes and cardiac remodeling after myocardial infarction
IntroductionInterleukin-10 (IL-10) is a potent immunomodulatory cytokine widely explored as a therapeutic agent for diseases, including myocardial infarction (MI). High-dose IL-10 treatment may not achieve expected outcomes, raising the question of whether IL-10 has dose-dependency, or even uncharte...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2024.1481460/full |
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| author | Jing J. Zhang Rodrigue Rizk Xiaoping Li Brandon G. Lee Mason L. Matthies Kennedy A. Bietz Kang Kim Kang Kim Kang Kim Johnny Huard Yadong Wang William C. W. Chen |
| author_facet | Jing J. Zhang Rodrigue Rizk Xiaoping Li Brandon G. Lee Mason L. Matthies Kennedy A. Bietz Kang Kim Kang Kim Kang Kim Johnny Huard Yadong Wang William C. W. Chen |
| author_sort | Jing J. Zhang |
| collection | DOAJ |
| description | IntroductionInterleukin-10 (IL-10) is a potent immunomodulatory cytokine widely explored as a therapeutic agent for diseases, including myocardial infarction (MI). High-dose IL-10 treatment may not achieve expected outcomes, raising the question of whether IL-10 has dose-dependency, or even uncharted side-effects from overdosing. We hypothesized that IL-10 has dose-dependent effects on macrophage (Mφ) phenotypic transition and cardiac remodeling after MI.MethodsUsing RAW264.7 monocyte models, we examined whether administering differential doses of exogenous IL-10 (0–1,000 ng/mL) perturbs classic M1 (pro-inflammatory) and M2 (anti-inflammatory) phenotypes of polarized Mφ or even alters the phenotypic transition of prospective M1 and M2 polarization. We then investigated the impact of single intramyocardial IL-10 administration on cardiac function, structure, and inflammation post-MI, using a mouse MI model.ResultsCompared with 0-ng/mL control, 250-ng/mL IL-10 had the strongest overall effects in decreasing M1 and increasing M2 phenotypes on polarized Mφ while ≥500-ng/mL IL-10 dampened M1 polarization and augmented native IL-10 secretion more effectively than low doses in vitro. Echocardiography revealed that the 250-ng group had consistently higher contractile function and lower left ventricular (LV) dilatation than the saline control over 6 weeks while ≥1,000-ng groups exhibited transient lower LV ejection fraction at 5 days post-MI in vivo. Moreover, different doses of IL-10 differentially modulated myocardial gene expression, phagocytic cell infiltration at the infarct, LV fibrosis, and revascularization post-MI, with some, but not all, doses exerting beneficial effects.DiscussionOur study suggested that IL-10 has an effective dose range on Mφ phenotypes, and intramyocardial IL-10 treatment may trigger cardioprotective or unwanted effects post-MI in a dose-dependent manner. |
| format | Article |
| id | doaj-art-e3aaf123686340af8b26016490064d78 |
| institution | Kabale University |
| issn | 1664-042X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Physiology |
| spelling | doaj-art-e3aaf123686340af8b26016490064d782025-01-15T06:10:24ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2025-01-011510.3389/fphys.2024.14814601481460Interleukin-10 exhibit dose-dependent effects on macrophage phenotypes and cardiac remodeling after myocardial infarctionJing J. Zhang0Rodrigue Rizk1Xiaoping Li2Brandon G. Lee3Mason L. Matthies4Kennedy A. Bietz5Kang Kim6Kang Kim7Kang Kim8Johnny Huard9Yadong Wang10William C. W. Chen11Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, United StatesDepartment of Computer Science, University of South Dakota, Vermillion, SD, United StatesDivision of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, United StatesDepartment of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, United StatesDivision of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, United StatesDivision of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, United StatesDepartment of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, United StatesCenter for Ultrasound Molecular Imaging and Therapeutics, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesMcGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesThe Linda & Mitch Center for Regenerative and Personalized Medicine, Steadman Philippon Research Institute, Vail, CO, United StatesThe Biofoundry, Department of Biomedical Engineering, Cornell University, Ithaca, NY, United StatesDivision of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, United StatesIntroductionInterleukin-10 (IL-10) is a potent immunomodulatory cytokine widely explored as a therapeutic agent for diseases, including myocardial infarction (MI). High-dose IL-10 treatment may not achieve expected outcomes, raising the question of whether IL-10 has dose-dependency, or even uncharted side-effects from overdosing. We hypothesized that IL-10 has dose-dependent effects on macrophage (Mφ) phenotypic transition and cardiac remodeling after MI.MethodsUsing RAW264.7 monocyte models, we examined whether administering differential doses of exogenous IL-10 (0–1,000 ng/mL) perturbs classic M1 (pro-inflammatory) and M2 (anti-inflammatory) phenotypes of polarized Mφ or even alters the phenotypic transition of prospective M1 and M2 polarization. We then investigated the impact of single intramyocardial IL-10 administration on cardiac function, structure, and inflammation post-MI, using a mouse MI model.ResultsCompared with 0-ng/mL control, 250-ng/mL IL-10 had the strongest overall effects in decreasing M1 and increasing M2 phenotypes on polarized Mφ while ≥500-ng/mL IL-10 dampened M1 polarization and augmented native IL-10 secretion more effectively than low doses in vitro. Echocardiography revealed that the 250-ng group had consistently higher contractile function and lower left ventricular (LV) dilatation than the saline control over 6 weeks while ≥1,000-ng groups exhibited transient lower LV ejection fraction at 5 days post-MI in vivo. Moreover, different doses of IL-10 differentially modulated myocardial gene expression, phagocytic cell infiltration at the infarct, LV fibrosis, and revascularization post-MI, with some, but not all, doses exerting beneficial effects.DiscussionOur study suggested that IL-10 has an effective dose range on Mφ phenotypes, and intramyocardial IL-10 treatment may trigger cardioprotective or unwanted effects post-MI in a dose-dependent manner.https://www.frontiersin.org/articles/10.3389/fphys.2024.1481460/fullinterleukin-10ischemic heart diseasemyocardial infarctionimmunomodulationmacrophage phenotypecardiac remodeling |
| spellingShingle | Jing J. Zhang Rodrigue Rizk Xiaoping Li Brandon G. Lee Mason L. Matthies Kennedy A. Bietz Kang Kim Kang Kim Kang Kim Johnny Huard Yadong Wang William C. W. Chen Interleukin-10 exhibit dose-dependent effects on macrophage phenotypes and cardiac remodeling after myocardial infarction Frontiers in Physiology interleukin-10 ischemic heart disease myocardial infarction immunomodulation macrophage phenotype cardiac remodeling |
| title | Interleukin-10 exhibit dose-dependent effects on macrophage phenotypes and cardiac remodeling after myocardial infarction |
| title_full | Interleukin-10 exhibit dose-dependent effects on macrophage phenotypes and cardiac remodeling after myocardial infarction |
| title_fullStr | Interleukin-10 exhibit dose-dependent effects on macrophage phenotypes and cardiac remodeling after myocardial infarction |
| title_full_unstemmed | Interleukin-10 exhibit dose-dependent effects on macrophage phenotypes and cardiac remodeling after myocardial infarction |
| title_short | Interleukin-10 exhibit dose-dependent effects on macrophage phenotypes and cardiac remodeling after myocardial infarction |
| title_sort | interleukin 10 exhibit dose dependent effects on macrophage phenotypes and cardiac remodeling after myocardial infarction |
| topic | interleukin-10 ischemic heart disease myocardial infarction immunomodulation macrophage phenotype cardiac remodeling |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2024.1481460/full |
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