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

Jennifer M Felton; David A Dorward; Jennifer Cartwright; Philippe M D  Potey; Calum T Robb; Jingang Gui; Ruth W Craig; Jurgen Schwarze; Christopher Haslett; Rodger Duffin; Ian Dransfield; Christopher D Lucas; Adriano G Rossi

doi:10.1136/thoraxjnl-2019-213204

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

Jennifer M Felton, David A Dorward, Jennifer Cartwright, Philippe M D Potey, Calum T Robb, Jingang Gui, Ruth W Craig, Jurgen Schwarze, Christopher Haslett, Rodger Duffin, Ian Dransfield, Christopher D Lucas, Adriano G Rossi

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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 Mcl-1 mice (hMcl-1) and reducing Mcl-1 by a cyclin-dependent kinase inhibitor.
Over-expression 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.

Original language	English
Pages (from-to)	600-605
Journal	Thorax
Volume	75
Issue number	7
Early online date	17 Apr 2020
DOIs	https://doi.org/10.1136/thoraxjnl-2019-213204
Publication status	Published - 1 Jul 2020

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thoraxjnl-2019-213204.full
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Final published version, 1.11 MBLicence: Creative Commons: Attribution (CC-BY)

Wellcome Trust Tissue Repair PhD Programme MAIN AWARD
Forbes, S., Hansen, C. & Rossi, A.
UK-based charities
11/09/17 → 30/09/23
Project: Research
Macrophage-epithelial communication promotes lung repair after injury
Lucas, C.
UK-based charities
3/07/17 → 4/08/22
Project: Research
The role of cyclin-dependent kinase-9 inhibition in promoting the resolution of chronic inflammation
Rossi, A. & Haslett, C.
MRC
1/05/13 → 30/10/19
Project: Research

Rodger Duffin
- Deanery of Clinical Sciences - Personal Chair of Thoracic Toxicology
- Centre for Inflammation Research
Person: Academic: Research Active

Cite this

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title = "Mcl-1 protects eosinophils from apoptosis and exacerbates allergic airway inflammation",

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 Mcl-1 mice (hMcl-1) and reducing Mcl-1 by a cyclin-dependent kinase inhibitor. Over-expression 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 = "Felton, {Jennifer M} and Dorward, {David A} and Jennifer Cartwright and Potey, {Philippe M D} and Robb, {Calum T} and Jingang Gui and Craig, {Ruth W} and Jurgen Schwarze and Christopher Haslett and Rodger Duffin and Ian Dransfield and Lucas, {Christopher D} and Rossi, {Adriano G}",

year = "2020",

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doi = "10.1136/thoraxjnl-2019-213204",

language = "English",

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T1 - Mcl-1 protects eosinophils from apoptosis and exacerbates allergic airway inflammation

AU - Felton, Jennifer M

AU - Dorward, David A

AU - Cartwright, Jennifer

AU - Potey, Philippe M D

AU - Robb, Calum T

AU - Gui, Jingang

AU - Craig, Ruth W

AU - Schwarze, Jurgen

AU - Haslett, Christopher

AU - Duffin, Rodger

AU - Dransfield, Ian

AU - Lucas, Christopher D

AU - Rossi, Adriano G

PY - 2020/7/1

Y1 - 2020/7/1

N2 - 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 Mcl-1 mice (hMcl-1) and reducing Mcl-1 by a cyclin-dependent kinase inhibitor. Over-expression 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.

AB - 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 Mcl-1 mice (hMcl-1) and reducing Mcl-1 by a cyclin-dependent kinase inhibitor. Over-expression 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.

U2 - 10.1136/thoraxjnl-2019-213204

DO - 10.1136/thoraxjnl-2019-213204

M3 - Article

SN - 0040-6376

VL - 75

SP - 600

EP - 605

JO - Thorax

JF - Thorax

IS - 7

ER -

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

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Projects

Wellcome Trust Tissue Repair PhD Programme MAIN AWARD

Macrophage-epithelial communication promotes lung repair after injury

The role of cyclin-dependent kinase-9 inhibition in promoting the resolution of chronic inflammation

Profiles

Rodger Duffin

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