[en] Heat shock transcription factor (HSF)-1 is recognized as a central component of the heat shock response, which protects against various harmful conditions. However, the mechanisms underlying the protection and the role of HSF-1 in these mechanisms have not yet been clearly elucidated. Using HSF-1 knockout mice (Hsf1_/_), we examined whether heat shock responsemediated lung protection involved an inhibition of the proinflammatory pathway via an interaction between HSF-1 and NF-_B, in response to cadmium insult. The HSF-1-dependent protective effect against intranasal instillation of cadmium (10 and 100 _g/mouse) was demonstrated by the higher protein content (1.2- and 1.4-fold), macrophage (1.6- and 1.9-fold), and neutrophil (2.6- and 1.8-fold) number in bronchoalveolar fluids, higher lung wet-to-dry weight ratio, and more severe lung damage evaluated by histopathology in Hsf1_/_compared with wild-type animals. These responses were associated with higher granulocyte/macrophage colony-stimulating factor (GMCSF; 1.7-fold) but not TNF-_ concentrations in bronchoalveolar fluids of Hsf1_/_ mice compared with those of wild-type animals, indicating that HSF-1 behaved as a repressor of specific cytokine production in our model. To further investigate the mechanism of GM-CSF repression, we analyzed the NF-_B activity and I_B stability. The DNA binding NF-_B activity, in particular p50 homodimer activity, was higher in Hsf1_/_ mice than in wild-type mice after cadmium exposure. These results provide a first line of evidence that mechanisms of lung protection depending on HSF-1 involve specific cytokine repression via inhibition of NF-_B activation in vivo.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Wirth, D.
Bureau, Fabrice ; Université de Liège - ULiège > Département de sciences fonctionnelles > GIGA-R : Biochimie et biologie moléculaire
Melotte, D.
Christians, E.
Gustin, Pascal ; Université de Liège - ULiège > Département de sciences fonctionnelles > Pharmacologie, pharmacothérapie et toxicologie
Language :
English
Title :
Evidence for a role of heat shock factor 1 in inhibition of NF-kB pathway during heat shock response-mediated lung protection
Publication date :
2004
Journal title :
American Journal of Physiology - Lung Cellular and Molecular Physiology
ISSN :
1040-0605
eISSN :
1522-1504
Publisher :
American Physiological Society, Bethesda, United States - Maryland
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