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Caspase-1 deficiency reduces eosinophilia and interleukin-33 in an asthma exacerbation model

Menzel, Mandy LU ; Akbarshahi, Hamid LU ; Mahmutovic Persson, Irma LU ; Puthia, Manoj LU ; Bjermer, Leif LU and Uller, Lena LU (2017) In ERJ Open Research 3(4).
Abstract

Rhinovirus infections are common triggers of asthma exacerbations. Viruses can activate the inflammasome, resulting in processing and activation of caspase-1. This recruitment triggers production of interleukin (IL)-1β and IL-18, which have been implicated in asthma. Elucidating the involvement of the inflammasome and its compartments, such as caspase-1, in asthma exacerbations is warranted. Gene expression of caspase-1 was measured in rhinovirus-infected primary bronchial epithelial cells of asthmatic and healthy donors 24 h post-infection. In an in vivo exacerbation experiment C57BL/6 wild-type and caspase-1-/- mice were challenged with house dust mite followed by exposures to the viral mimic poly(I:C). General lung inflammatory... (More)

Rhinovirus infections are common triggers of asthma exacerbations. Viruses can activate the inflammasome, resulting in processing and activation of caspase-1. This recruitment triggers production of interleukin (IL)-1β and IL-18, which have been implicated in asthma. Elucidating the involvement of the inflammasome and its compartments, such as caspase-1, in asthma exacerbations is warranted. Gene expression of caspase-1 was measured in rhinovirus-infected primary bronchial epithelial cells of asthmatic and healthy donors 24 h post-infection. In an in vivo exacerbation experiment C57BL/6 wild-type and caspase-1-/- mice were challenged with house dust mite followed by exposures to the viral mimic poly(I:C). General lung inflammatory parameters and levels of T-helper type 2 (Th2)-upstream cytokines IL-33, thymic stromal lymphopoietin (TSLP) and IL-25 were assessed. Caspase-1 expression was elevated after rhinoviral infection exclusively in bronchial epithelial cells from asthmatics. In a translational mouse model of asthma exacerbation effects of caspase-1 on airway inflammation and Th2-upstream cytokines were explored. Caspase-1 deficient mice exhibited no alterations of general lung inflammatory parameters, but showed markedly reduced eosinophilia. Furthermore, the Th2-upstream cytokines IL-33, TSLP and IL-25 were reduced at exacerbation in mice lacking caspase-1. Rhinovirus infection increases bronchial epithelial caspase-1 in asthma. Caspase-1 may induce production of lung Th2-upstream cytokines and eosinophilia at exacerbations. Further targeting of caspase-1 signalling is warranted to explore its role in asthma exacerbations.

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Contribution to journal
publication status
published
subject
in
ERJ Open Research
volume
3
issue
4
publisher
European Respiratory Society
external identifiers
  • scopus:85071912777
  • pmid:29204432
ISSN
2312-0541
DOI
10.1183/23120541.00047-2017
language
English
LU publication?
yes
id
5557af93-a332-44de-8040-a64c54f50a7e
date added to LUP
2017-12-12 10:54:20
date last changed
2025-01-08 03:04:41
@article{5557af93-a332-44de-8040-a64c54f50a7e,
  abstract     = {{<p>Rhinovirus infections are common triggers of asthma exacerbations. Viruses can activate the inflammasome, resulting in processing and activation of caspase-1. This recruitment triggers production of interleukin (IL)-1β and IL-18, which have been implicated in asthma. Elucidating the involvement of the inflammasome and its compartments, such as caspase-1, in asthma exacerbations is warranted. Gene expression of caspase-1 was measured in rhinovirus-infected primary bronchial epithelial cells of asthmatic and healthy donors 24 h post-infection. In an in vivo exacerbation experiment C57BL/6 wild-type and caspase-1-/- mice were challenged with house dust mite followed by exposures to the viral mimic poly(I:C). General lung inflammatory parameters and levels of T-helper type 2 (Th2)-upstream cytokines IL-33, thymic stromal lymphopoietin (TSLP) and IL-25 were assessed. Caspase-1 expression was elevated after rhinoviral infection exclusively in bronchial epithelial cells from asthmatics. In a translational mouse model of asthma exacerbation effects of caspase-1 on airway inflammation and Th2-upstream cytokines were explored. Caspase-1 deficient mice exhibited no alterations of general lung inflammatory parameters, but showed markedly reduced eosinophilia. Furthermore, the Th2-upstream cytokines IL-33, TSLP and IL-25 were reduced at exacerbation in mice lacking caspase-1. Rhinovirus infection increases bronchial epithelial caspase-1 in asthma. Caspase-1 may induce production of lung Th2-upstream cytokines and eosinophilia at exacerbations. Further targeting of caspase-1 signalling is warranted to explore its role in asthma exacerbations.</p>}},
  author       = {{Menzel, Mandy and Akbarshahi, Hamid and Mahmutovic Persson, Irma and Puthia, Manoj and Bjermer, Leif and Uller, Lena}},
  issn         = {{2312-0541}},
  language     = {{eng}},
  number       = {{4}},
  publisher    = {{European Respiratory Society}},
  series       = {{ERJ Open Research}},
  title        = {{Caspase-1 deficiency reduces eosinophilia and interleukin-33 in an asthma exacerbation model}},
  url          = {{http://dx.doi.org/10.1183/23120541.00047-2017}},
  doi          = {{10.1183/23120541.00047-2017}},
  volume       = {{3}},
  year         = {{2017}},
}