Differential heat shock gene hsp70-1 response to toxicants revealed by in vivo study of lungs in transgenic mice

Wirth, Delphine; Christians, Elisabeth; Munaut, Carine; Dessy, Cécile; Foidart, Jean‐Michel; Gustin, Pascal

doi:10.1379/1466-1268(2002)007<0387:dhsghr>2.0.co;2

Cited by 32 publications

(23 citation statements)

References 40 publications

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“…[14][15][16][17] We developed a transgenic model based on our previous Hsp70A1-luc construct, but with a dual reporter comprised of firefly luciferase and enhanced green fluorescent protein (eGFP) joined by the 2A "ribosome slippage site" from the foot and mouth disease virus (FMDV) (Hsp70A1-luc-2A-GFP). 3,9,18,19 This dual reporter construct was designed to enable macroscopic analysis of an Hsp70 expression in vivo via luciferase expression using BLI and microscopic assays using eGFP.…”

Section: Pulse Duration Determines Levels Of Hsp70 Induction In Tissumentioning

confidence: 99%

Pulse duration determines levels of Hsp70 induction in tissues following laser irradiation

Mackanos

Contag

2011

J. Biomed. Opt.

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Abstract. Induction of heat shock protein (Hsp) expression correlates with cytoprotection, reduced tissue damage, and accelerated healing in animal models. Since Hsps are transcriptionally activated in response to stress, they can act as stress indicators in burn injury or surgical procedures that produce heat and thermal change. A fast in vivo readout for induction of Hsp transcription in tissues would allow for the study of these proteins as therapeutic effect mediators and reporters of thermal stress/damage. We used a transgenic reporter mouse in which a luciferase expression is controlled by the regulatory region of the inducible 70 kilodalton (kDa) Hsp as a rapid readout of cellular responses to laser-mediated thermal stress/injury in mouse skin. We assessed the pulse duration dependence of the Hsp70 expression after irradiation with a CO 2 laser at 10.6 μm in wavelength over a range of 1000 to 1 ms. Hsp70 induction varied with changes in laser pulse durations and radiant exposures, which defined the ranges at which thermal activation of Hsp70 can be used to protect cells from subsequent stress, and reveals the window of thermal stress that tissues can endure. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

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Section: Pulse Duration Determines Levels Of Hsp70 Induction In Tissumentioning

confidence: 99%

Pulse duration determines levels of Hsp70 induction in tissues following laser irradiation

Mackanos

Contag

2011

J. Biomed. Opt.

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“…Interestingly, this heavy metal is also known as a strong inducer of the HS response (15,41). The protective role of HSF-1 against Cd-induced lung injuries has been recently identified (40), but the possible interactions between HSF-1 and proinflammatory pathways were not known.…”

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confidence: 99%

Evidence for a role of heat shock factor 1 in inhibition of NF-κB pathway during heat shock response-mediated lung protection

Wirth

Bureau

Mélotte³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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Wirth, Delphine, Fabrice Bureau, Dorothée Melotte, Elisabeth Christians, and Pascal Gustin. Evidence for a role of heat shock factor 1 in inhibition of NF-B pathway during heat shock responsemediated lung protection. Am J Physiol Lung Cell Mol Physiol 287: L953-L961, 2004. First published June 25, 2004 doi:10.1152/ ajplung.00184.2003.-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 Ϫ/Ϫ ), 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 Ϫ/Ϫ compared with wild-type animals. These responses were associated with higher granulocyte/macrophage colony-stimulating factor (GM-CSF; 1.7-fold) but not TNF-␣ concentrations in bronchoalveolar fluids of Hsf1 Ϫ/Ϫ 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 IB stability. The DNA binding NF-B activity, in particular p50 homodimer activity, was higher in Hsf1 Ϫ/Ϫ 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. knockout mice; cadmium; heat shock proteins; granulocyte/macrophage colony-stimulating factor; nuclear factor-B

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“…Transgenic mice have been used for toxicologic analyses; for example, to test genotoxicity (103) or to signal the presence of toxic inorganic compounds through reporter gene expression driven by hsp70 promoter (104,105). Other models are planned for the evaluation of the enzymatic system responsible for drug metabolism in the liver (102,106).…”

Section: Transgenic Animalsmentioning

confidence: 99%

Molecular-Genetic Imaging Based on Reporter Gene Expression

Kang¹,

Chung²

2008

J Nucl Med

208

178

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Molecular imaging includes proteomic, metabolic, cellular biologic process, and genetic imaging. In a narrow sense, molecular imaging means genetic imaging and can be called moleculargenetic imaging. Imaging reporter genes play a leading role in molecular-genetic imaging. There are 3 major methods of molecular-genetic imaging, based on optical, MRI, and nuclear medicine modalities. For each of these modalities, various reporter genes and probes have been developed, and these have resulted in successful transitions from bench to bedside applications. Each of these imaging modalities has its unique advantages and disadvantages. Fluorescent and bioluminescent optical imaging modalities are simple, less expensive, more convenient, and more user friendly than other imaging modalities. Another advantage, especially of bioluminescence imaging, is its ability to detect low levels of gene expression. MRI has the advantage of high spatial resolution, whereas nuclear medicine methods are highly sensitive and allow data from small-animal imaging studies to be translated to clinical practice. Moreover, multimodality imaging reporter genes will allow us to choose the imaging technologies that are most appropriate for the biologic problem at hand and facilitate the clinical application of reporter gene technologies. Reporter genes can be used to visualize the levels of expression of particular exogenous and endogenous genes and several intracellular biologic phenomena, including specific signal transduction pathways, nuclear receptor activities, and protein-protein interactions. This technique provides a straightforward means of monitoring tumor mass and can visualize the in vivo distributions of target cells, such as immune cells and stem cells. Molecular imaging has gradually evolved into an important tool for drug discovery and development, and transgenic mice with an imaging reporter gene can be useful during drug and stem cell therapy development. Moreover, instrumentation improvements, the identification of novel targets and genes, and imaging probe developments suggest that molecular-genetic imaging is likely to play an increasingly important role in the diagnosis and therapy of cancer.

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Differential heat shock gene hsp70-1 response to toxicants revealed by in vivo study of lungs in transgenic mice

Cited by 32 publications

References 40 publications

Pulse duration determines levels of Hsp70 induction in tissues following laser irradiation

Pulse duration determines levels of Hsp70 induction in tissues following laser irradiation

Evidence for a role of heat shock factor 1 in inhibition of NF-κB pathway during heat shock response-mediated lung protection

Molecular-Genetic Imaging Based on Reporter Gene Expression

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