| Autor: |
Jing Lu, Jiaming meng, Gang Wu, Wulong Wei, Huabao Xie, Yanli Liu |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Molecular Medicine, Vol 30, Iss 1, Pp 1-14 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1528-3658 |
| DOI: |
10.1186/s10020-024-00882-z |
| Popis: |
Abstract Background and aims Inflammation is initiates the propagation phase of aortic valve calcification. The activation of NLRP3 signaling in macrophages plays a crucial role in the progression of calcific aortic valve stenosis (CAVS). IFN-γ regulates NLRP3 activity in macrophages. This study aimed to explore the mechanism of IFN-γ regulation and its impact on CAVS progression and valve interstitial cell transdifferentiation. Methods and results The number of Th1 cells and the expression of IFN-γ and STAT1 in the aortic valve, spleen and peripheral blood increased significantly as CAVS progressed. To explore the mechanisms underlying the roles of Th1 cells and IFN-γ, we treated CAVS mice with IFN-γ-AAV9 or an anti-IFN-γ neutralizing antibody. While IFN-γ promoted aortic valve calcification and dysfunction, it significantly decreased NLRP3 signaling in splenic macrophages and Ly6C+ monocytes. In vitro coculture showed that Th1 cells inhibited NLPR3 activation in ox-LDL-treated macrophages through the IFN-γR1/IFN-γR2-STAT1 pathway. Compared with untreated medium, conditioned medium from Th1-treated bone marrow–derived macrophages reduced the osteogenic calcification of valvular interstitial cells. Conclusion Inhibition of the NLRP3 inflammasome by Th1 cells protects against valvular interstitial cell calcification as a negative feedback mechanism of adaptive immunity toward innate immunity. This study provides a precision medicine strategy for CAVS based on the targeting of anti-inflammatory mechanisms. Graphical Abstract |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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