Photoactivated adenylyl cyclases attenuate sepsis-induced cardiomyopathy by suppressing macrophage-mediated inflammation
Sepsis-induced myocardiopathy, characterized by innate immune cells infiltration and proinflammatory cytokines release, may lead to perfusion failure or even life-threatening cardiogenic shock. Macrophages-mediated inflammation has been shown to contribute to sepsis-induced myocardiopathy. In the cu...
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| Format: | Article |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1008702/full |
| _version_ | 1817982979375366144 |
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| author | Guofang Xia Hongyu Shi Yuanyuan Su Beibei Han Chengxing Shen Shiqiang Gao Zhong Chen Congfeng Xu |
| author_facet | Guofang Xia Hongyu Shi Yuanyuan Su Beibei Han Chengxing Shen Shiqiang Gao Zhong Chen Congfeng Xu |
| author_sort | Guofang Xia |
| collection | DOAJ |
| description | Sepsis-induced myocardiopathy, characterized by innate immune cells infiltration and proinflammatory cytokines release, may lead to perfusion failure or even life-threatening cardiogenic shock. Macrophages-mediated inflammation has been shown to contribute to sepsis-induced myocardiopathy. In the current study, we introduced two photoactivated adenylyl cyclases (PACs), Beggiatoa sp. PAC (bPAC) and Beggiatoa sp. IS2 PAC (biPAC) into macrophages by transfection to detect the effects of light-induced regulation of macrophage pro-inflammatory response and LPS-induced sepsis-induced myocardiopathy. By this method, we uncovered that blue light-induced bPAC or biPAC activation considerably inhibited the production of pro-inflammatory cytokines IL-1 and TNF-α, both at mRNA and protein levels. Further, we assembled a GelMA-Macrophages-LED system, which consists of GelMA—a type of light crosslink hydrogel, gene modulated macrophages and wireless LED device, to allow light to regulate cardiac inflammation in situ with murine models of LPS-induced sepsis. Our results showed significant inhibition of leukocytes infiltration, especially macrophages and neutrophils, suppression of pro-inflammatory cytokines release, and alleviation of sepsis-induced cardiac dysfunction. Thus, our study may represent an emerging means to treat sepsis-induced myocardiopathy and other cardiovascular diseases by photo-activated regulating macrophage function. |
| first_indexed | 2024-04-13T23:27:08Z |
| format | Article |
| id | doaj.art-71cad9b506294a578f940c4eecd6a46c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T23:27:08Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-71cad9b506294a578f940c4eecd6a46c2022-12-22T02:25:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.10087021008702Photoactivated adenylyl cyclases attenuate sepsis-induced cardiomyopathy by suppressing macrophage-mediated inflammationGuofang Xia0Hongyu Shi1Yuanyuan Su2Beibei Han3Chengxing Shen4Shiqiang Gao5Zhong Chen6Congfeng Xu7Department of Cardiology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaWusong Central Hospital, Shanghai, ChinaDepartment of Cardiology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaInstitute of Physiology, Department of Neurophysiology, Julius-Maximilians-University of Wuerzburg, Wuerzburg, GermanyDepartment of Cardiology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaSepsis-induced myocardiopathy, characterized by innate immune cells infiltration and proinflammatory cytokines release, may lead to perfusion failure or even life-threatening cardiogenic shock. Macrophages-mediated inflammation has been shown to contribute to sepsis-induced myocardiopathy. In the current study, we introduced two photoactivated adenylyl cyclases (PACs), Beggiatoa sp. PAC (bPAC) and Beggiatoa sp. IS2 PAC (biPAC) into macrophages by transfection to detect the effects of light-induced regulation of macrophage pro-inflammatory response and LPS-induced sepsis-induced myocardiopathy. By this method, we uncovered that blue light-induced bPAC or biPAC activation considerably inhibited the production of pro-inflammatory cytokines IL-1 and TNF-α, both at mRNA and protein levels. Further, we assembled a GelMA-Macrophages-LED system, which consists of GelMA—a type of light crosslink hydrogel, gene modulated macrophages and wireless LED device, to allow light to regulate cardiac inflammation in situ with murine models of LPS-induced sepsis. Our results showed significant inhibition of leukocytes infiltration, especially macrophages and neutrophils, suppression of pro-inflammatory cytokines release, and alleviation of sepsis-induced cardiac dysfunction. Thus, our study may represent an emerging means to treat sepsis-induced myocardiopathy and other cardiovascular diseases by photo-activated regulating macrophage function.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1008702/fullmacrophagephotoactivated adenylyl cyclaseinflammationoptogeneticssepsis-induced myocardiopathycell-based therapy |
| spellingShingle | Guofang Xia Hongyu Shi Yuanyuan Su Beibei Han Chengxing Shen Shiqiang Gao Zhong Chen Congfeng Xu Photoactivated adenylyl cyclases attenuate sepsis-induced cardiomyopathy by suppressing macrophage-mediated inflammation Frontiers in Immunology macrophage photoactivated adenylyl cyclase inflammation optogenetics sepsis-induced myocardiopathy cell-based therapy |
| title | Photoactivated adenylyl cyclases attenuate sepsis-induced cardiomyopathy by suppressing macrophage-mediated inflammation |
| title_full | Photoactivated adenylyl cyclases attenuate sepsis-induced cardiomyopathy by suppressing macrophage-mediated inflammation |
| title_fullStr | Photoactivated adenylyl cyclases attenuate sepsis-induced cardiomyopathy by suppressing macrophage-mediated inflammation |
| title_full_unstemmed | Photoactivated adenylyl cyclases attenuate sepsis-induced cardiomyopathy by suppressing macrophage-mediated inflammation |
| title_short | Photoactivated adenylyl cyclases attenuate sepsis-induced cardiomyopathy by suppressing macrophage-mediated inflammation |
| title_sort | photoactivated adenylyl cyclases attenuate sepsis induced cardiomyopathy by suppressing macrophage mediated inflammation |
| topic | macrophage photoactivated adenylyl cyclase inflammation optogenetics sepsis-induced myocardiopathy cell-based therapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1008702/full |
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