Caratti, G;
Poolman, T;
Hurst, RJ;
Ince, L;
Knight, A;
Krakowiak, K;
Durrington, HJ;
... Ray, DW; + view all
(2019)
Caveolin1 interacts with the glucocorticoid receptor in the lung but is dispensable for its anti-inflammatory actions in lung inflammation and Trichuris Muris infection.
Scientific Reports
, 9
, Article 8581. 10.1038/s41598-019-44963-0.
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Caveolin1 interacts with the glucocorticoid receptor in the lung but is dispensable for its anti-inflammatory actions in lun.pdf - Published Version Download (5MB) | Preview |
Abstract
Glucocorticoids (Gcs) are widely prescribed anti-inflammatory compounds, which act through the glucocorticoid receptor (GR). Using an unbiased proteomics screen in lung tissue, we identified the membrane protein caveolin -1 (Cav1) as a direct interaction partner of the GR. In Cav1 knockout mice GR transactivates anti-inflammatory genes, including Dusp1, more than in controls. We therefore determined the role of Cav1 in modulating Gc action in two models of pulmonary inflammation. We first tested innate responses in lung. Loss of Cav1 impaired the inflammatory response to nebulized LPS, increasing cytokine/chemokine secretion from lung, but impairing neutrophil infiltration. Despite these changes to the inflammatory response, there was no Cav1 effect on anti-inflammatory capacity of Gcs. We also tested GR/Cav1 crosstalk in a model of allergic airway inflammation. Cav1 had a very mild effect on the inflammatory response, but no effect on the Gc response – with comparable immune cell infiltrate (macrophage, eosinophils, neutrophils), pathological score and PAS positive cells observed between both genotypes. Pursuing the Th2 adaptive immune response further we demonstrate that Cav1 knockout mice retained their ability to expel the intestinal nematode parasite T.muris, which requires adaptive Th2 immune response for elimination. Therefore, Cav1 regulates innate immune responses in the lung, but does not have an effect on Th2-mediated adaptive immunity in lung or gut. Although we demonstrate that Cav1 regulates GR transactivation of anti-inflammatory genes, this does not translate to an effect on suppression of inflammation in vivo.
| Type: | Article |
|---|---|
| Title: | Caveolin1 interacts with the glucocorticoid receptor in the lung but is dispensable for its anti-inflammatory actions in lung inflammation and Trichuris Muris infection |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41598-019-44963-0 |
| Publisher version: | https://doi.org/10.1038/s41598-019-44963-0 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Acute inflammation, Protein–protein interaction networks |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10103183 |
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