Mcl-1保护嗜酸性粒细胞免于凋亡并加剧过敏性气道炎症
2020/08/20
摘要
嗜酸性粒细胞是过敏性气道疾病的关键免疫细胞。本文使用转基因高表达人Mcl-1小鼠（hMcl-1），通过细胞周期蛋白依赖性激酶抑制剂来降低Mcl-1，我们研究了Mcl-1（一种抗凋亡蛋白）在实验性过敏性气道炎症中的作用。Mcl-1的过表达加剧了过敏性气道炎症，支气管肺泡灌洗液细胞数、嗜酸性粒细胞数和总蛋白增加，气道粘液分泌增加。Mcl-1的过表达抑制了嗜酸性粒细胞的凋亡，通过抑制细胞周期蛋白依赖性激酶减弱了嗜酸性粒细胞对凋亡的抵抗，这也挽救了Mcl-1加重的过敏性气道炎症。我们认为靶向Mcl-1可能有助于治疗过敏性气道疾病。
Mcl-1 protects eosinophils from apoptosis and exacerbates allergic airway inflammation
Jennifer M Felton , David A Dorward , Jennifer A Cartwright , Philippe Md Potey , Calum T Robb , Jingang Gui, Ruth W Craig , Jürgen Schwarze , Christopher Haslett , Rodger Duffin , Ian Dransfield , Christopher D Lucas , Adriano G Rossi
Abstract
Eosinophils are key effector cells in allergic diseases. Here we investigated Mcl-1 (an anti-apoptotic protein) in experimental allergic airway inflammation using transgenic overexpressing human Mcl-1 mice (hMcl-1) and reducing Mcl-1 by a cyclin-dependent kinase inhibitor. Overexpression of Mcl-1 exacerbated allergic airway inflammation, with increased bronchoalveolar lavage fluid cellularity, eosinophil numbers and total protein, and an increase in airway mucus production. Eosinophil apoptosis was suppressed by Mcl-1 overexpression, with this resistance to apoptosis attenuated by cyclin-dependent kinase inhibition which also rescued Mcl-1-exacerbated allergic airway inflammation. We propose that targeting Mcl-1 may be beneficial in treatment of allergic airway disease.
嗜酸性粒细胞是过敏性气道疾病的关键免疫细胞。本文使用转基因高表达人Mcl-1小鼠（hMcl-1），通过细胞周期蛋白依赖性激酶抑制剂来降低Mcl-1，我们研究了Mcl-1（一种抗凋亡蛋白）在实验性过敏性气道炎症中的作用。Mcl-1的过表达加剧了过敏性气道炎症，支气管肺泡灌洗液细胞数、嗜酸性粒细胞数和总蛋白增加，气道粘液分泌增加。Mcl-1的过表达抑制了嗜酸性粒细胞的凋亡，通过抑制细胞周期蛋白依赖性激酶减弱了嗜酸性粒细胞对凋亡的抵抗，这也挽救了Mcl-1加重的过敏性气道炎症。我们认为靶向Mcl-1可能有助于治疗过敏性气道疾病。
(中日友好医院呼吸与危重症医学科 张清 摘译 林江涛 审校)
(Thorax. 2020 Jul;75(7):600-605. doi: 10.1136/thoraxjnl-2019-213204. Epub 2020 Apr 17.)
(Thorax. 2020 Jul;75(7):600-605. doi: 10.1136/thoraxjnl-2019-213204. Epub 2020 Apr 17.)
Mcl-1 protects eosinophils from apoptosis and exacerbates allergic airway inflammation
Jennifer M Felton , David A Dorward , Jennifer A Cartwright , Philippe Md Potey , Calum T Robb , Jingang Gui, Ruth W Craig , Jürgen Schwarze , Christopher Haslett , Rodger Duffin , Ian Dransfield , Christopher D Lucas , Adriano G Rossi
Abstract
Eosinophils are key effector cells in allergic diseases. Here we investigated Mcl-1 (an anti-apoptotic protein) in experimental allergic airway inflammation using transgenic overexpressing human Mcl-1 mice (hMcl-1) and reducing Mcl-1 by a cyclin-dependent kinase inhibitor. Overexpression of Mcl-1 exacerbated allergic airway inflammation, with increased bronchoalveolar lavage fluid cellularity, eosinophil numbers and total protein, and an increase in airway mucus production. Eosinophil apoptosis was suppressed by Mcl-1 overexpression, with this resistance to apoptosis attenuated by cyclin-dependent kinase inhibition which also rescued Mcl-1-exacerbated allergic airway inflammation. We propose that targeting Mcl-1 may be beneficial in treatment of allergic airway disease.
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