Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/43409

OpenURL Link
Title
Glutathione transferase P1: an endogenous inhibitor of allergic responses in a mouse model of asthma
Author/Creator
Zhou, Jiansheng;  Wolf, C. Roland;  Henderson, Colin J.;  Cai, Yeping;  Board, Philip G.;  Foster, Paul S.;  Webb, Dianne C.
Institution
The University of Newcastle. Faculty of Health, School of Biomedical Sciences and Pharmacy
Description
Rationale: Although epidemiological studies have linked asthma susceptibility and severity to polymorphisms in human glutathione transferase Pi (GSTP) 1, there is no direct evidence for a functional involvement of GSTP1 in processes that are pathognomic of asthma. Objectives: To examine the role of GSTP1 in modulating the development of allergic airways disease. Methods: Allergic airways disease was induced in wild-type (WT) and Gstp-null mice employing both acute and chronic models. Eosinophilia, goblet cells, and remodeling were quantified by histological assessment; respiratory function was determined using invasive methods. ELISA was used to evaluate Th2 cytokines, eotaxin, and phospho-c-Jun. Gstp1/2 expression was quantified by reverse transcriptase–polymerase chain reaction. Measurements and Main Results: Compared with allergic WT mice, eosinophilia, goblet cell hyperplasia, airway remodeling, lung resistance, and IL-5 were enhanced in allergic Gstp-null mice. However, the protective efficacy of GSTP1 was mouse-strain dependent, and associated with inherent variation in expression of Gstp1. Although elevated levels of phospho-c-Jun were detected in Gstp-null mice, treatment of WT mice with a GSTP/c-Jun N-terminal kinase (JNK) inhibitory peptide enhanced phospho-c-Jun and significantly attenuated allergic responses. Conclusions: GSTP1 attenuates the severity of allergic airways disease. However, the efficacy of GSTP1 correlated with mouse strain-dependent variation in Gstp1 expression. Although GSTP1 attenuated c-Jun phosphorylation, treatment with a GSTP/JNK inhibitory peptide revealed an inverse relationship between c-Jun phosphorylation and allergic responses, indicating that the mechanism by which GSTP attenuates allergic responses is not dependent on the JNK/c-Jun axis. Our data, together with epidemiological evidence, suggest variation in expression and/or function of this protein is an important determinant in asthma pathophysiology.
Relation
American Journal of Respiratory and Critical Care Medicine Vol. 178, Issue 12, p. 1202-1210
Publisher Link
http://dx.doi.org/10.1164/rccm.200801-178OC
Date
2008
Publisher
American Thoracic Society
Keyword(s)
asthma;  oxidative stress;  Th2 cytokines;  JNK
Resource Type
journal article
Identifier
http://hdl.handle.net/1959.13/43409
Identifier
ISSN:1073-449X
Reviewed
Reviewed
9 Visitors 13 Hits 0 Downloads
Save/E-mail Citation
Citation Format
E-mail Address
Subject
"American Journal of Respiratory and Critical Care Medicine"
 
OR