Frontiers in immunology · 2025
Pharmacological inhibition of IL12β is effective in treating pressure overload-induced cardiac inflammation and heart failure.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Bhattarai Umesh, He Xiaochen, Niu Ziru, Pan Lihong, Wang Dongzhi, Wang Hao, Zeng Heng, Chen Jian-Xiong, Speed Joshua S, Clemmer John S, Chen Yingjie
Аннотация
BACKGROUND AND OBJECTIVE: Emerging evidence indicates that inflammation regulates cardiac remodeling and heart failure (HF). IL12β is a subunit for proinflammatory cytokines IL12 and IL23. However, the effect of IL12β inhibition on HF development and the underlying mechanism is not understood.
METHODS: We determined the effect of pharmacological inhibition of IL12β using IL12β blocking antibody on transverse aortic constriction (TAC)-induced left ventricular (LV) inflammation and HF development.
RESULTS: IL12β blocking antibody significantly attenuated TAC-induced LV immune cell infiltration, hypertrophy, fibrosis, dysfunction, and the consequent pulmonary inflammation and remodeling. More specifically, we found that IL12β blocking antibody significantly attenuated TAC-induced LV and pulmonary infiltration of neutrophils, macrophages, CD11c+ dendritic cells, CD8+ T cells, and CD4+ T cells. Moreover, IL12β blocking antibody significantly suppressed the production of pro-inflammatory cytokine pro-IL1β and IFNγ by macrophages and IFNγ by CD8+ T cells and/or CD4+ T cells.
CONCLUSIONS: These findings indicate that pharmacological inhibition of IL12β effectively protected the heart from systolic overload-induced inflammation, remodeling, and dysfunction by reducing the proinflammatory signaling from both innate and adaptive immune responses.
METHODS: We determined the effect of pharmacological inhibition of IL12β using IL12β blocking antibody on transverse aortic constriction (TAC)-induced left ventricular (LV) inflammation and HF development.
RESULTS: IL12β blocking antibody significantly attenuated TAC-induced LV immune cell infiltration, hypertrophy, fibrosis, dysfunction, and the consequent pulmonary inflammation and remodeling. More specifically, we found that IL12β blocking antibody significantly attenuated TAC-induced LV and pulmonary infiltration of neutrophils, macrophages, CD11c+ dendritic cells, CD8+ T cells, and CD4+ T cells. Moreover, IL12β blocking antibody significantly suppressed the production of pro-inflammatory cytokine pro-IL1β and IFNγ by macrophages and IFNγ by CD8+ T cells and/or CD4+ T cells.
CONCLUSIONS: These findings indicate that pharmacological inhibition of IL12β effectively protected the heart from systolic overload-induced inflammation, remodeling, and dysfunction by reducing the proinflammatory signaling from both innate and adaptive immune responses.