Linked Life Data

21094186

Source:http://linkedlifedata.com/resource/pubmed/id/21094186

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2011-1-25
pubmed:abstractText
Heat shock protein 72 (Hsp72), a canonical intracellular molecular chaperone, may also function as an extracellular danger signal for the innate immune system. To further delineate the biological role of Hsp72 in the innate immune system, we generated two truncated versions of the full length human Hsp72 (N-terminus Hsp72, amino acids 1-430; and C-terminus Hsp72 amino acids 420-641) and directly compared their ability to activate cells from the macrophage/monocyte lineage. In RAW 264.7 macrophages transfected with a NF-?B-dependent luciferase reporter plasmid, C-terminus Hsp72 was a more potent inducer of NF-?B activity than N-terminus Hsp72, and this effect did not seem to be secondary to endotoxin contamination. C-terminus Hsp72-mediated activation of the NF-?B pathway was corroborated by increased activation of I?B kinase, degradation of I?B?, and increased NF-?B-DNA binding. C-terminus Hsp72 was a more potent inducer of tumor necrosis factor-? (TNF?) expression in RAW 264.7 macrophages and in primary murine peritoneal macrophages from wild-type mice. C-terminus Hsp72 did not induce TNF? expression in primary murine peritoneal macrophages from Toll-like receptor (TLR4) mutant mice, indicating a role for TLR4. In human THP-1 mononuclear cells, C-terminus Hsp72 induced tolerance to subsequent LPS stimulation, whereas N-terminus Hsp72 did not induce tolerance. Finally, control experiments using equimolar amounts of N-terminus or C-terminus Hsp72 demonstrated a higher biological potency for C-terminus Hsp72. These data demonstrate that the ability of human Hsp72 to serve as an activator for cells of the macrophage/monocyte lineage primarily lies in the C-terminus region spanning amino acids 420-641.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1879-0542
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
30
pubmed:volume
135
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
173-9
pubmed:dateRevised
2011-10-6
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Biological activity of truncated C-terminus human heat shock protein 72.
pubmed:affiliation
Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural