| First Author | Li X | Year | 2022 |
| Journal | Oxid Med Cell Longev | Volume | 2022 |
| Pages | 5719974 | PubMed ID | 36225174 |
| Mgi Jnum | J:330022 | Mgi Id | MGI:7355594 |
| Doi | 10.1155/2022/5719974 | Citation | Li X, et al. (2022) Macrophage-Derived Exosomes in TLR9(-/-) Mice Ameliorate Sepsis-Induced Mitochondrial Oxidative Stress and Apoptosis in Cardiomyocytes. Oxid Med Cell Longev 2022:5719974 |
| abstractText | Objective: To explore the mechanisms of TLR9 from macrophages on mitochondrial apoptosis in cardiomyocytes at early stage of sepsis. Methods: The in vivo and in vitro sepsis mice were bone marrow transplantation (BMT) with wild type (WT) or (toll-like receptor 9) TLR9 knockout ((-/-) or KO) myeloid cells and then constructed by cecum ligation and puncture (CLP) as vivo experiment and cardiomyocytes cocultured with WT or TLR9-deficient macrophages treated with LPS as vitro experiment, respectively. Sepsis model were performed by CLP. The expression levels of exosome, PI3K/AKT, and ERK1/2, inflammatory factors, and apoptotic proteins were tested by western blot in vivo. Besides, associated apoptotic proteins and JC-1 fluorescence assay were tested in vitro. Results: The expressions of p-PI3K, p-AKT, exosome markers (CD9, CD63, and TSG101), p-ERK1/2, TNF-alpha, IFN-gamma, IL-1beta, and cleaved-caspase-3/-9 were significantly increased in septic mice vs. control mice, and these proteins were declined dramatically in TLR9(-/-) BMT mice vs. WT BMT mice in sepsis mice models. Meanwhile, the protein expression of cytochrome C, cleaved-caspase-3, and cleaved-caspase-9 increased significantly in primary mouse myocardial cells cocultured with TLR9(-/-) or WT macrophages stimulated with LPS, and these mitochondrial apoptotic proteins as well as the green 5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimidazolcarbocyanine iodide (JC-1) fluorescence were dramatically lower in LPS-stimulated cardiomyocytes cocultured with TLR9(-/-) than with WT macrophages. Conclusion: TLR9(-/-) in macrophages suppressed the inflammatory reaction as well as the exosome secretion and resulted in the inhibition of apoptosis and oxidative stress in sepsis-induced cardiomyopathy. |
