International immunopharmacology · 2023
Hypoxia induces the production of epithelial-derived cytokines in eosinophilic chronic rhinosinusitis with nasal polyps.
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.
Zhang Meiping, Tang Binxiang, Huang Ligui, Xiong Yishan, Tu Junhao, Jia Yizhen, Jiang Fan, Shen Li, Luo Qing, Ye Jing
Аннотация
BACKGROUND: Hypoxia plays a significant role in the pathogenesis of chronic rhinosinusitis (CRS). However, the role and mechanism of hypoxia in the type 2 immune response in eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) remain unclear.
METHODS: The expression of hypoxia-inducible factor-1α (HIF-1α) and epithelial-derived cytokines (EDCs), including interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP), was detected in nasal polyps via immunohistochemical analysis. The relationship between HIF-1α and EDCs was also elucidated using Pearson's correlation. Moreover, primary human nasal epithelial cells (HNECs) and a mouse model of ECRSwNP were employed to elucidate the role and mechanism of hypoxia in type 2 immune responses.
RESULTS: HIF-1α, IL-25, IL-33, and TSLP expression levels were upregulated in the non-ECRSwNP and ECRSwNP groups compared with the control group, with the ECRSwNP group having the highest HIF-1α and EDC expression levels. Additionally, HIF-1α was positively correlated with IL-25 and IL-33 in the ECRSwNP group. Meanwhile, treatment with a HIF-1α inhibitor, PX-478, inhibited the hypoxia-induced increase in the mRNA and protein expression of EDCs and type 2 cytokines in HNECs. Similarly, in vivo, PX-478 inhibited EDC expression in the sinonasal mucosa of mice with ECRSwNP.
CONCLUSIONS: Hypoxia induces EDC expression by upregulating HIF-1α levels, thereby promoting type 2 immune responses and the development of ECRSwNP. Hence, targeting HIF-1α may represent an effective therapeutic strategy for ECRSwNP.
METHODS: The expression of hypoxia-inducible factor-1α (HIF-1α) and epithelial-derived cytokines (EDCs), including interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP), was detected in nasal polyps via immunohistochemical analysis. The relationship between HIF-1α and EDCs was also elucidated using Pearson's correlation. Moreover, primary human nasal epithelial cells (HNECs) and a mouse model of ECRSwNP were employed to elucidate the role and mechanism of hypoxia in type 2 immune responses.
RESULTS: HIF-1α, IL-25, IL-33, and TSLP expression levels were upregulated in the non-ECRSwNP and ECRSwNP groups compared with the control group, with the ECRSwNP group having the highest HIF-1α and EDC expression levels. Additionally, HIF-1α was positively correlated with IL-25 and IL-33 in the ECRSwNP group. Meanwhile, treatment with a HIF-1α inhibitor, PX-478, inhibited the hypoxia-induced increase in the mRNA and protein expression of EDCs and type 2 cytokines in HNECs. Similarly, in vivo, PX-478 inhibited EDC expression in the sinonasal mucosa of mice with ECRSwNP.
CONCLUSIONS: Hypoxia induces EDC expression by upregulating HIF-1α levels, thereby promoting type 2 immune responses and the development of ECRSwNP. Hence, targeting HIF-1α may represent an effective therapeutic strategy for ECRSwNP.