大麻素受体2作为油酰乙醇酰胺在嗜酸性粒细胞哮喘中诱导的炎症调节剂
2023/12/20
摘要
背景：据报道，油酰乙醇酰胺 （OEA） 是一种内源性产生的大麻素样化合物，在严重哮喘和阿司匹林加重的呼吸系统疾病患者中会增加。气道中活化的嗜酸性粒细胞募集是支气管哮喘的标志。
目的：探讨大麻素受体2 (cannabinoid receptor 2, CB2)在体外和体内诱导嗜酸性粒细胞活化的直接作用。
方法：我们研究了哮喘患者外周血嗜酸性粒细胞dEol-1嗜酸性粒细胞中的OEA信号。为了确认OEA激活嗜酸性粒细胞是否依赖CB2，我们使用了CB2 siRNA和CB2拮抗剂SR144528。测定BALB/c小鼠支气管肺泡灌洗液中气道炎症细胞数量和细胞因子水平，并检测气道高反应性。
结果：经OEA处理后，外周血嗜酸性粒细胞和dEol-1细胞中CB2表达均升高。在体内，OEA诱导的嗜酸性粒细胞向肺募集后也升高。然而，SR144528治疗降低了哮喘患者外周血嗜酸性粒细胞的激活。此外，CB2敲除降低了dEol-1细胞的激活以及炎症和T2细胞因子的水平。SR144528治疗在体内减轻了气道的高反应性和嗜酸性粒细胞向肺部的募集。
结论：这些结果表明，CB2可能有助于嗜酸性粒细胞性哮喘的发病机制。我们的研究结果为OEA在嗜酸性粒细胞性哮喘中信号转导的分子机制提供了新的见解。
Cannabinoid receptor 2 as a regulator of inflammation induced by oleoylethanolamide in eosinophilic asthma.
Kwon EK, Choi Y, Sim S,
Abstrast
Background: Oleoylethanolamide (OEA), an endogenously generated cannabinoid-like compound, has been reported to be increased in patients with severe asthma and aspirin-exacerbated respiratory disease. Recruitment of activated eosinophils in the airways is a hallmark of bronchial asthma.
Objective：To explore the direct contribution of cannabinoid receptor 2 (CB2), a cognate receptor of OEA, which induces of eosinophil activation in vitro and in vivo.
Methods: We investigated OEA signaling in the eosinophilic cell line dEol-1, in peripheral blood eosinophils from asthmatics. In order to confirm whether eosinophil activation by OEA is CB2 dependent or not, CB2 siRNA and the CB2 antagonist SR144528 were used. The numbers of airway inflammatory cells and the levels of cytokines were measured in bronchoalveolar lavage fluid, and airway hyper-responsiveness were examined in the BALB/c mice.
Results：CB2 expression was increased after OEA treatment in both peripheral blood eosinophils and dEol-1 cells. It was also elevated after OEA-induced recruitment of eosinophils to the lungs in vivo. However, SR144528 treatment reduced the activation of peripheral blood eosinophils from asthmatic patients. Furthermore, CB2 knockdown decreased the activation of dEol-1 cells and the levels of inflammatory and T2 cytokines. SR144528 treatment alleviated airway hyper-responsiveness and eosinophil recruitment to the lungs in vivo.
Conclusions: These results suggest that CB2 may contribute to the pathogenesis of eosinophilic asthma. Our results provide a new insight into the molecular mechanism of signal transduction by OEA in eosinophilic asthma.
背景：据报道，油酰乙醇酰胺 （OEA） 是一种内源性产生的大麻素样化合物，在严重哮喘和阿司匹林加重的呼吸系统疾病患者中会增加。气道中活化的嗜酸性粒细胞募集是支气管哮喘的标志。
目的：探讨大麻素受体2 (cannabinoid receptor 2, CB2)在体外和体内诱导嗜酸性粒细胞活化的直接作用。
方法：我们研究了哮喘患者外周血嗜酸性粒细胞dEol-1嗜酸性粒细胞中的OEA信号。为了确认OEA激活嗜酸性粒细胞是否依赖CB2，我们使用了CB2 siRNA和CB2拮抗剂SR144528。测定BALB/c小鼠支气管肺泡灌洗液中气道炎症细胞数量和细胞因子水平，并检测气道高反应性。
结果：经OEA处理后，外周血嗜酸性粒细胞和dEol-1细胞中CB2表达均升高。在体内，OEA诱导的嗜酸性粒细胞向肺募集后也升高。然而，SR144528治疗降低了哮喘患者外周血嗜酸性粒细胞的激活。此外，CB2敲除降低了dEol-1细胞的激活以及炎症和T2细胞因子的水平。SR144528治疗在体内减轻了气道的高反应性和嗜酸性粒细胞向肺部的募集。
结论：这些结果表明，CB2可能有助于嗜酸性粒细胞性哮喘的发病机制。我们的研究结果为OEA在嗜酸性粒细胞性哮喘中信号转导的分子机制提供了新的见解。
(中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校)
(J Allergy Clin Immunol 2023 Dec 05; doi: 10.1016/j.jaci.2023.09.043. IF：10.228.)
(J Allergy Clin Immunol 2023 Dec 05; doi: 10.1016/j.jaci.2023.09.043. IF：10.228.)
Cannabinoid receptor 2 as a regulator of inflammation induced by oleoylethanolamide in eosinophilic asthma.
Kwon EK, Choi Y, Sim S,
Abstrast
Background: Oleoylethanolamide (OEA), an endogenously generated cannabinoid-like compound, has been reported to be increased in patients with severe asthma and aspirin-exacerbated respiratory disease. Recruitment of activated eosinophils in the airways is a hallmark of bronchial asthma.
Objective：To explore the direct contribution of cannabinoid receptor 2 (CB2), a cognate receptor of OEA, which induces of eosinophil activation in vitro and in vivo.
Methods: We investigated OEA signaling in the eosinophilic cell line dEol-1, in peripheral blood eosinophils from asthmatics. In order to confirm whether eosinophil activation by OEA is CB2 dependent or not, CB2 siRNA and the CB2 antagonist SR144528 were used. The numbers of airway inflammatory cells and the levels of cytokines were measured in bronchoalveolar lavage fluid, and airway hyper-responsiveness were examined in the BALB/c mice.
Results：CB2 expression was increased after OEA treatment in both peripheral blood eosinophils and dEol-1 cells. It was also elevated after OEA-induced recruitment of eosinophils to the lungs in vivo. However, SR144528 treatment reduced the activation of peripheral blood eosinophils from asthmatic patients. Furthermore, CB2 knockdown decreased the activation of dEol-1 cells and the levels of inflammatory and T2 cytokines. SR144528 treatment alleviated airway hyper-responsiveness and eosinophil recruitment to the lungs in vivo.
Conclusions: These results suggest that CB2 may contribute to the pathogenesis of eosinophilic asthma. Our results provide a new insight into the molecular mechanism of signal transduction by OEA in eosinophilic asthma.
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