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

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

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

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 endotoxinmediated 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 LPSinduced 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 IKBa degradation and nuclear factor kappa-B (NF-κB) p65 nuclear translocation in liver, suggesting that HSP70 over expression 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.

Original languageEnglish (US)
Pages (from-to)153-163
Number of pages11
JournalCell Stress and Chaperones
Volume15
Issue number2
DOIs
StatePublished - Mar 2010

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology

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