An initial assessment of the involvement of transglutaminase2 in eosinophilic bronchitis using a disease model developed in C57BL/6 mice

Abstract The detailed pathogenesis of eosinophilic bronchitis (EB) remains unclear. Transglutaminase 2 (TG2) has been implicated in many respiratory diseases including asthma. Herein, we aim to assess preliminarily the relationship of TG2 with EB in the context of the development of an appropriate E...

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Autores principales: Lan Chen, Shuyan Liu, Linzhuo Xiao, Kanyao Chen, Juanjuan Tang, Chuqin Huang, Wei Luo, Dominique Ferrandon, Kefang Lai, Zi Li
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:d531bb2643a44d93bf49b29edc12765a2021-12-02T17:47:23ZAn initial assessment of the involvement of transglutaminase2 in eosinophilic bronchitis using a disease model developed in C57BL/6 mice10.1038/s41598-021-90950-92045-2322https://doaj.org/article/d531bb2643a44d93bf49b29edc12765a2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90950-9https://doaj.org/toc/2045-2322Abstract The detailed pathogenesis of eosinophilic bronchitis (EB) remains unclear. Transglutaminase 2 (TG2) has been implicated in many respiratory diseases including asthma. Herein, we aim to assess preliminarily the relationship of TG2 with EB in the context of the development of an appropriate EB model through ovalbumin (OVA) sensitization and challenge in the C57BL/6 mouse strain. Our data lead us to propose a 50 μg dose of OVA challenge as appropriate to establish an EB model in C57BL/6 mice, whereas a challenge with a 400 μg dose of OVA significantly induced asthma. Compared to controls, TG2 is up-regulated in the airway epithelium of EB mice and EB patients. When TG2 activity was inhibited by cystamine treatment, there were no effects on airway responsiveness; in contrast, the lung pathology score and eosinophil counts in bronchoalveolar lavage fluid were significantly increased whereas the cough frequency was significantly decreased. The expression levels of interleukin (IL)-4, IL-13, IL-6, mast cell protease7 and the transient receptor potential (TRP) ankyrin 1 (TRPA1), TRP vanilloid 1 (TRPV1) were significantly decreased. These data open the possibility of an involvement of TG2 in mediating the increased cough frequency in EB through the regulation of TRPA1 and TRPV1 expression. The establishment of an EB model in C57BL/6 mice opens the way for a genetic investigation of the involvement of TG2 and other molecules in this disease using KO mice, which are often generated in the C57BL/6 genetic background.Lan ChenShuyan LiuLinzhuo XiaoKanyao ChenJuanjuan TangChuqin HuangWei LuoDominique FerrandonKefang LaiZi LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Lan Chen
Shuyan Liu
Linzhuo Xiao
Kanyao Chen
Juanjuan Tang
Chuqin Huang
Wei Luo
Dominique Ferrandon
Kefang Lai
Zi Li
An initial assessment of the involvement of transglutaminase2 in eosinophilic bronchitis using a disease model developed in C57BL/6 mice
description Abstract The detailed pathogenesis of eosinophilic bronchitis (EB) remains unclear. Transglutaminase 2 (TG2) has been implicated in many respiratory diseases including asthma. Herein, we aim to assess preliminarily the relationship of TG2 with EB in the context of the development of an appropriate EB model through ovalbumin (OVA) sensitization and challenge in the C57BL/6 mouse strain. Our data lead us to propose a 50 μg dose of OVA challenge as appropriate to establish an EB model in C57BL/6 mice, whereas a challenge with a 400 μg dose of OVA significantly induced asthma. Compared to controls, TG2 is up-regulated in the airway epithelium of EB mice and EB patients. When TG2 activity was inhibited by cystamine treatment, there were no effects on airway responsiveness; in contrast, the lung pathology score and eosinophil counts in bronchoalveolar lavage fluid were significantly increased whereas the cough frequency was significantly decreased. The expression levels of interleukin (IL)-4, IL-13, IL-6, mast cell protease7 and the transient receptor potential (TRP) ankyrin 1 (TRPA1), TRP vanilloid 1 (TRPV1) were significantly decreased. These data open the possibility of an involvement of TG2 in mediating the increased cough frequency in EB through the regulation of TRPA1 and TRPV1 expression. The establishment of an EB model in C57BL/6 mice opens the way for a genetic investigation of the involvement of TG2 and other molecules in this disease using KO mice, which are often generated in the C57BL/6 genetic background.
format article
author Lan Chen
Shuyan Liu
Linzhuo Xiao
Kanyao Chen
Juanjuan Tang
Chuqin Huang
Wei Luo
Dominique Ferrandon
Kefang Lai
Zi Li
author_facet Lan Chen
Shuyan Liu
Linzhuo Xiao
Kanyao Chen
Juanjuan Tang
Chuqin Huang
Wei Luo
Dominique Ferrandon
Kefang Lai
Zi Li
author_sort Lan Chen
title An initial assessment of the involvement of transglutaminase2 in eosinophilic bronchitis using a disease model developed in C57BL/6 mice
title_short An initial assessment of the involvement of transglutaminase2 in eosinophilic bronchitis using a disease model developed in C57BL/6 mice
title_full An initial assessment of the involvement of transglutaminase2 in eosinophilic bronchitis using a disease model developed in C57BL/6 mice
title_fullStr An initial assessment of the involvement of transglutaminase2 in eosinophilic bronchitis using a disease model developed in C57BL/6 mice
title_full_unstemmed An initial assessment of the involvement of transglutaminase2 in eosinophilic bronchitis using a disease model developed in C57BL/6 mice
title_sort initial assessment of the involvement of transglutaminase2 in eosinophilic bronchitis using a disease model developed in c57bl/6 mice
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/d531bb2643a44d93bf49b29edc12765a
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