Document Detail

The role of endogenously produced extracellular hsp72 in mononuclear cell reprogramming.
MedLine Citation:
PMID:  18323737     Owner:  NLM     Status:  MEDLINE    
Intracellular heat shock protein 72 (Hsp72) is known to serve a broad cytoprotective role. Recent data indicate that stressed cells can release Hsp72 into the extracellular compartment, although the biological function of extracellular Hsp72 remains to be fully elucidated. Because extracellular Hsp72 has been demonstrated to interact with Toll-like receptor 4, we hypothesized that endogenously produced and released Hsp72 would reprogram the mononuclear cell responses to LPS. THP-1 cells treated with LPS were used as a model for nuclear factor (NF)-kappaB activation. Heat shock conditions consisted of incubation at 43 degrees C for 1 h. Control cells were incubated at 37 degrees C. Twenty four hours after incubation, heat shock conditioned media (HSCM) and control media (CM) were centrifuged, and the respective cells were discarded. A separate group of naive THP-1 cells were then incubated with either HSCM or CM for 18 h and then stimulated with LPS (1 mug/mL). Heat shock significantly increased Hsp72 in HSCM compared with CM. In THP-1 cells transfected with an NF-kappaB luciferase reporter plasmid, the addition of HSCM attenuated subsequent LPS-mediated luciferase activity compared with cells incubated in CM. The addition of HSCM also attenuated LPS-mediated NF-kappaB-DNA binding and IkappaBalpha degradation. Heat shock protein 72-mediated inhibition of NF-kappaB activation was further corroborated by a significant decrease in TNF-alpha production. When HSCM and CM were subjected to Hsp72 depletion via adenosine triphosphate-agarose binding, LPS-mediated activation of NF-kappaB was partially restored, suggesting that Hsp72 is partially responsible for cellular reprogramming in response to HSCM. These data demonstrate that endogenously produced and released extracellular Hsp72 has the ability to reprogram the in vitro response to endotoxin in cultured human mononuclear cells.
Patricia A Abboud; Patrick M Lahni; Kristen Page; John S Giuliano; Kelli Harmon; Katherine E Dunsmore; Hector R Wong; Derek S Wheeler
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  30     ISSN:  1540-0514     ISO Abbreviation:  Shock     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-18     Completed Date:  2008-12-09     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  United States    
Other Details:
Languages:  eng     Pagination:  285-92     Citation Subset:  IM    
Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
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MeSH Terms
Anoxia / metabolism
Cell Line, Tumor
Endotoxins / metabolism
HSP72 Heat-Shock Proteins / metabolism*
Immune System
Ischemic Preconditioning
Leukocytes, Mononuclear / metabolism*
Lipopolysaccharides / metabolism
Models, Biological
Monocytes / metabolism
NF-kappa B / metabolism
Sepharose / chemistry
Signal Transduction
Grant Support
K08 GM077432/GM/NIGMS NIH HHS; K08 GM077432-04/GM/NIGMS NIH HHS; R01 GM061723/GM/NIGMS NIH HHS; R01 GM061723-07/GM/NIGMS NIH HHS
Reg. No./Substance:
0/Endotoxins; 0/HSP72 Heat-Shock Proteins; 0/Lipopolysaccharides; 0/NF-kappa B; 9012-36-6/Sepharose

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