Mcl-1 protects eosinophils from apoptosis and exacerbates allergic airway inflammation.

Thorax 2020 Jul

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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. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

Citation

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. Mcl-1 protects eosinophils from apoptosis and exacerbates allergic airway inflammation. Thorax. 2020 Jul;75(7):600-605