Article (Scientific journals)
Use of Hsf1(-/-) mice reveals an essential role for HSF1 to protect lung against cadmium-induced injury
Wirth, D.; Christians, E.; Li, Xiang et al.
2003In Toxicology and Applied Pharmacology, 192 (1), p. 12-20
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Keywords :
knockout mice; cadmium; heat-shock proteins; heat-shock factor 1
Abstract :
[en] Cadmium (Cd) is known to activate heat shock (HS) response, which is characterized by overexpression of heat shock proteins (Hsps) under the control of heat shock factor 1 (HSF1). The potential protection provided by the HS response, induced by increasing the body temperature of animals before Cd exposure or by Cd itself, against pathophysiological changes occurring after Cd intranasal instillation (1 to 100 microg/mouse) was examined. HSF1-deficient mice were used to evaluate the role of this factor in lung protection. Cd instillation caused dose- and time-dependent changes in the respiratory pattern measured by plethysmography (Penh), and significant increases in lactate dehydrogenase (LDH) activity as well as macrophage and neutrophil counts in bronchoalveolar lavage fluids. HS preconditioning induced Hsp overexpression and reduced the Penh (-30%), LDH (-25%), and neutrophil (-55%) responses to subsequent administration of the highest Cd doses (50 and 100 microg) in wild-type mice. HSF1 deficiency abolished the HS response and its protective effect. In the absence of preconditioning, Hsf1(-/-) mice exhibited higher values of Penh (+70%) and LDH activity (+42%) compared with wild-type animals when exposed to the lowest Cd doses. Higher macrophage (+80%) and neutrophil counts (+115%) were recorded whatever the dose. Western blot analyses indicated that lung protection might be related to the kinetics of HSF1-dependent Hsp70 expression. Altogether, our data demonstrate that HS response elicited both by prior HS and by Cd itself moderates pulmonary injuries due to Cd instillation, and that HSF1 is a major mediator in this protection.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Wirth, D.
Christians, E.
Li, Xiang ;  Université de Liège - ULiège > Département Argenco : Secteur MS2F > Mécanique des solides
Benjamin, I. J.
Gustin, Pascal ;  Université de Liège - ULiège > Département de sciences fonctionnelles > Pharmacologie, pharmacothérapie et toxicologie
Language :
English
Title :
Use of Hsf1(-/-) mice reveals an essential role for HSF1 to protect lung against cadmium-induced injury
Publication date :
2003
Journal title :
Toxicology and Applied Pharmacology
ISSN :
0041-008X
eISSN :
1096-0333
Publisher :
Academic Press Inc Elsevier Science, San Diego, United States - California
Volume :
192
Issue :
1
Pages :
12-20
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 30 January 2017

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