The role of endogenously produced extracellular HSP72 in mononuclear cell reprogramming

Patricia A. Abboud, Patrick M. Lahni, Kristen Page, John S. Giuliano, Kelli Harmon, Katherine E. Dunsmore, Hector R. Wong, Derek S. Wheeler

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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)-κB activation. Heat shock conditions consisted of incubation at 43°C for 1 h. Control cells were incubated at 37°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 μg/mL). Heat shock significantly increased Hsp72 in HSCM compared with CM. In THP-1 cells transfected with an NF-κB 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-κB-DNA binding and IκBα degradation. Heat shock protein 72-mediated inhibition of NF-κB activation was further corroborated by a significant decrease in TNF-α production. When HSCM and CM were subjected to Hsp72 depletion via adenosine triphosphate-agarose binding, LPS-mediated activation of NF-κB 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.

Original languageEnglish (US)
Pages (from-to)285-292
Number of pages8
JournalShock
Volume30
Issue number3
DOIs
StatePublished - Sep 2008

Keywords

  • Endotoxin tolerance
  • Heat shock proteins
  • Inflammation
  • LPS
  • Monocytes
  • NF-κB
  • Preconditioning
  • Signal transduction

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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