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Heat shock factor 1 inhibits nuclear factor-κB nuclear binding activity during endotoxin tolerance and heat shock

Song, M and Pinsky, MR and Kellum, JA (2008) Heat shock factor 1 inhibits nuclear factor-κB nuclear binding activity during endotoxin tolerance and heat shock. Journal of Critical Care, 23 (3). 406 - 415. ISSN 0883-9441

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Rationale: Sepsis, endotoxin tolerance, and heat shock (HS) all display down-regulation of innate immunity. We hypothesize that HS factor 1 (HSF-1) induces competitive inhibition of nuclear factor-κB (NF-κB)-induced signal transduction in both endotoxin tolerance and HS. Objectives: We compared endotoxin tolerance and HS in RAW 264.7 cells. We transfected cells with an HS protein 70 (HSP70) plasmid to test whether HSP70 is the mediator of HS-induced NF-κB inhibition. We studied the effects of endotoxin stimulation and HS, both separately and together, on "wild-type" cells, cells transfected with the HSP70 plasmid, and cells transfected with vehicle. Findings: Heat shock protein 70 plasmid-transfected cells had increased HSP70 expression and demonstrated decreased nitric oxide (NO) release and inducible NO synthase messenger RNA expression in response to endotoxin compared with wild-type and empty plasmid-transfected cells. Heat shock completely abolished subsequent NO and inducible NO synthase messenger RNA expression in wild-type cells. Heat shock factor 1 reached maximum expression 60 to 90 minutes after HS. Heat shock protein 70-transfected cells still displayed endotoxin-induced NF-κB nuclear binding, whereas endotoxin tolerance, HS, and exposure to HSF-1, but not exposure to an unrelated promoter, inhibited NF-κB nuclear binding. Conclusions: Endotoxin tolerance and HS appear to share a common immune suppressive effect, possibly through HSF-1-mediated competitive inhibition of NF-κB nuclear binding. © 2008 Elsevier Inc. All rights reserved.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Song, M
Pinsky, MRpinsky@pitt.eduPINSKY0000-0001-6166-700X
Kellum, JAkellum@pitt.eduKELLUM0000-0003-1995-2653
Date: 1 September 2008
Date Type: Publication
Journal or Publication Title: Journal of Critical Care
Volume: 23
Number: 3
Page Range: 406 - 415
DOI or Unique Handle: 10.1016/j.jcrc.2007.09.007
Schools and Programs: School of Medicine > Critical Care Medicine
Refereed: Yes
ISSN: 0883-9441
PubMed ID: 18725048
Date Deposited: 05 Mar 2012 17:20
Last Modified: 30 Jan 2020 16:55


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