Abstract

Background: Glucocorticoid (GC) is the first-line therapy for asthma, but some asthmatics are insensitive to it. Glucocorticoid-induced transcript 1 gene (GLCCI1) is reported to be associated with GCs efficiency in asthmatics, while its exact mechanism remains unknown. Methods: A total of 30 asthmatic patients received fluticasone propionate for 12 weeks. Forced expiratory volume in 1 s (FEV1) and GLCCI1 expression were detected. Asthma model was constructed in wild-type and GLCCI1 knockout (GLCCI1-/-) mice. Glucocorticoid receptor (GR) and mitogen-activated protein kinase phosphatase 1 (MKP-1) expression were detected by polymerase chain reaction and Western blotting (WB). The phosphorylation of p38 mitogen-activated protein kinase (MAPK) was also detected by WB. Results: In asthmatic patients, the change of FEV1was well positively correlated with change of GLCCI1 expression (r = 0.430, P = 0.022). In animal experiment, GR and MKP-1 mRNA levels were significantly decreased in asthmatic mice than in control mice (wild-type: GR: 0.769 vs. 1.000, P = 0.022; MKP-1: 0.493 vs. 1.000, P < 0.001. GLCCI1-/-: GR: 0.629 vs. 1.645, P < 0.001; MKP-1: 0.377 vs. 2.146, P < 0.001). Hydroprednisone treatment significantly increased GR and MKP-1 mRNA expression levels than in asthmatic groups; however, GLCCI1-/-asthmatic mice had less improvement (wild-type: GR: 1.517 vs. 0.769, P = 0.023; MKP-1: 1.036 vs. 0.493, P = 0.003. GLCCI1-/-: GR: 0.846 vs. 0.629, P = 0.116; MKP-1: 0.475 vs. 0.377, P = 0.388). GLCCI1-/-asthmatic mice had more obvious phosphorylation of p38 MAPK than wild-type asthmatic mice (9.060 vs. 3.484, P < 0.001). It was still higher even though after hydroprednisone treatment (6.440 vs. 2.630, P < 0.001). Conclusions: GLCCI1 deficiency in asthmatic mice inhibits the activation of GR and MKP-1 and leads to more obvious phosphorylation of p38 MAPK, leading to a decremental sensitivity to GCs. Trial Registration: ChiCTR.org.cn, ChiCTR-RCC-13003634;http://www.chictr.org.cn/showproj.aspx?proj=5926.

Details

Title
Effects of Glucocorticoid-Induced Transcript 1 Gene Deficiency on Glucocorticoid Activation in Asthmatic Mice
Author
Cheng-Ping, Hu 1 ; Qiu-Fen Xun 2 ; Xiao-Zhao, Li 3 ; Xin-Yue, Hu 1 ; Qin, Ling 1 ; Ruo-Xi He 1 ; Jun-Tao, Feng 1 

 Department of Respiratory and Critical Care Medicine, Key Cite of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan 410008 
 Department of Respiratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006 
 Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan 410008 
Pages
2817-2826
Publication year
2018
Publication date
Dec 5, 2018
Publisher
Lippincott Williams & Wilkins Ovid Technologies
ISSN
03666999
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2150357210
Copyright
© 2018. This work is published under https://creativecommons.org/licenses/by-nc-sa/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.