PMID- 34099759 OWN - NLM STAT- MEDLINE DCOM- 20211108 LR - 20240226 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 11 IP - 1 DP - 2021 Jun 7 TI - An initial assessment of the involvement of transglutaminase2 in eosinophilic bronchitis using a disease model developed in C57BL/6 mice. PG - 11946 LID - 10.1038/s41598-021-90950-9 [doi] LID - 11946 AB - 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 mug dose of OVA challenge as appropriate to establish an EB model in C57BL/6 mice, whereas a challenge with a 400 mug 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. FAU - Chen, Lan AU - Chen L AD - Sino-French Hoffmann Institute, Guangzhou, China. FAU - Liu, Shuyan AU - Liu S AD - Sino-French Hoffmann Institute, Guangzhou, China. FAU - Xiao, Linzhuo AU - Xiao L AD - Sino-French Hoffmann Institute, Guangzhou, China. FAU - Chen, Kanyao AU - Chen K AD - Sino-French Hoffmann Institute, Guangzhou, China. FAU - Tang, Juanjuan AU - Tang J AD - Sino-French Hoffmann Institute, Guangzhou, China. FAU - Huang, Chuqin AU - Huang C AD - State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou Medical University, Guangzhou, China. FAU - Luo, Wei AU - Luo W AD - State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou Medical University, Guangzhou, China. FAU - Ferrandon, Dominique AU - Ferrandon D AD - Sino-French Hoffmann Institute, Guangzhou, China. AD - State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou Medical University, Guangzhou, China. AD - Universite de Strasbourg, M3I UPR9022 du CNRS, 67000, Strasbourg, France. FAU - Lai, Kefang AU - Lai K AD - State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou Medical University, Guangzhou, China. klai@163.com. FAU - Li, Zi AU - Li Z AD - Sino-French Hoffmann Institute, Guangzhou, China. lizi1002@gzhmu.edu.cn. AD - State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou Medical University, Guangzhou, China. lizi1002@gzhmu.edu.cn. LA - eng PT - Journal Article DEP - 20210607 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Cytokines) RN - 0 (TRPA1 Cation Channel) RN - 0 (Trpa1 protein, mouse) RN - 9006-59-1 (Ovalbumin) RN - EC 2.3.2.13 (Protein Glutamine gamma Glutamyltransferase 2) RN - EC 2.3.2.13 (Transglutaminases) RN - EC 3.6.1.- (GTP-Binding Proteins) RN - R110LV8L02 (Cystamine) SB - IM MH - Animals MH - Asthma/chemically induced/immunology MH - Bronchitis/chemically induced/*immunology/metabolism MH - Cystamine/pharmacology MH - Cytokines/genetics/immunology/metabolism MH - *Disease Models, Animal MH - Eosinophils/drug effects/*immunology/metabolism MH - GTP-Binding Proteins/genetics/*immunology/metabolism MH - Gene Expression Regulation/drug effects MH - Humans MH - Inflammation/genetics/immunology/metabolism MH - Lung/drug effects/immunology/pathology MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Ovalbumin MH - Protein Glutamine gamma Glutamyltransferase 2 MH - TRPA1 Cation Channel/genetics/immunology/metabolism MH - Transglutaminases/genetics/*immunology/metabolism MH - Mice PMC - PMC8184915 COIS- The authors declare no competing interests. EDAT- 2021/06/09 06:00 MHDA- 2021/11/09 06:00 PMCR- 2021/06/07 CRDT- 2021/06/08 06:22 PHST- 2020/10/14 00:00 [received] PHST- 2021/05/12 00:00 [accepted] PHST- 2021/06/08 06:22 [entrez] PHST- 2021/06/09 06:00 [pubmed] PHST- 2021/11/09 06:00 [medline] PHST- 2021/06/07 00:00 [pmc-release] AID - 10.1038/s41598-021-90950-9 [pii] AID - 90950 [pii] AID - 10.1038/s41598-021-90950-9 [doi] PST - epublish SO - Sci Rep. 2021 Jun 7;11(1):11946. doi: 10.1038/s41598-021-90950-9.