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LPS-induced cytokine levels are repressed by elevated expression of HSP70 in rats: possible role of NF-κB

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Cell Stress and Chaperones Aims and scope

Abstract

Heat shock protein (HSP)70 provides a spectrum of protection against any of a variety of stresses, preventing damage measured at the level of molecules, cells, as well as whole organism. We have previously reported that lipopolysaccharide (LPS)-induced lethality in rats is prevented by a previous exposure to a mild thermal stress and that a thermal stress sufficient to induce HSP70 expression in the liver is accompanied by an inhibition of endotoxin-mediated cytokines and modulation of febrile response. However, the effect of HSP70 upregulation on cytokine expression in animals is unknown. The aim of the present study was to demonstrate the effect of HSP70 overexpression with adenovirus administration on LPS-induced increase in cytokines levels in animals. In the present study, Sprague–Dawley rats were infected with either the control AdTrack or Ad70 virus that directs the expression of human HSP70. After a 5-day incubation, animals were injected with either saline alone or LPS (50 μg/kg). Four hours later, blood samples were drawn and plasma levels of interleukin (IL)-6 or tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assay. Our data demonstrate for the first time that HSP70 overexpression with adenovirus injection prevented the LPS-induced increase in TNF-α and IL-6 levels in rats. Repression of LPS-induced cytokines expressions by HSP70 upregulation was associated with inhibited IκBα degradation and nuclear factor kappa-B (NF-κB) p65 nuclear translocation in liver, suggesting that HSP70 overexpression may regulate LPS-induced cytokines expression through NF-κB pathway. We conclude that the effects of heat stress-induced increase in HSP70 protein expression on LPS-induced cytokine elaboration in whole animals can be reproduced by the actions of a single gene product.

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Acknowledgment

This work was supported by National Institutes of Health Grant AR40771 the NIEHS Center Grant P30-ES012072. The authors thank Dr. N. Kanagy for the use of the telemetry equipment.

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  1. Department of Internal Medicine, University of New Mexico Health Sciences Center, MSC 10-5550, Albuquerque, NM, 87131, USA

    Karol Dokladny, Rebecca Lobb, Walker Wharton, Thomas Y. Ma & Pope L. Moseley

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  1. Karol Dokladny
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  2. Rebecca Lobb
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  5. Pope L. Moseley
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Correspondence to Pope L. Moseley.

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Dokladny, K., Lobb, R., Wharton, W. et al. LPS-induced cytokine levels are repressed by elevated expression of HSP70 in rats: possible role of NF-κB. Cell Stress and Chaperones 15, 153–163 (2010). https://doi.org/10.1007/s12192-009-0129-6

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  • DOI: https://doi.org/10.1007/s12192-009-0129-6

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