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The relationship between apoptosis and high-mobility group protein 1 release from murine macrophages stimulated with lipopolysaccharide or polyinosinic-polycytidylic acid.

Publication ,  Journal Article
Jiang, W; Bell, CW; Pisetsky, DS
Published in: J Immunol
May 15, 2007

High-mobility group protein 1 (HMGB1) is a nonhistone nuclear protein whose function depends on cellular location. Inside the cell, HMGB1 modulates a variety of important cellular processes, including transcription, whereas outside the cell, HMGB1 acts as a cytokine that can promote inflammation and mediate sepsis and arthritis in animal models. In in vitro studies, proinflammatory molecules such as LPS, lipoteichoic acid, polyinosinic-polycytidylic acid (poly(I:C)), TNF-alpha, and type I and II IFNs can induce HMGB1 release from macrophages. Although these agents can activate cells, they can also induce apoptosis under certain circumstances. Therefore, because of evidence that apoptotic as well as necrotic cells can contribute to HMGB1-mediated events in sepsis, we have investigated the relationship between apoptosis and HMGB1 release in macrophages and other cells. In these experiments, using RAW 264.7 cells as a model, LPS and poly(I:C) caused HMGB1 release into the medium whereas CpG ODN failed to induce this response. With both LPS and poly(I:C), the extent of HMGB1 release correlated with the occurrence of apoptosis as measured by caspase 3 activation, lactate dehydrogenase release, and TUNEL staining. Similar results were obtained with primary murine macrophages as well as human Jurkat T cells. For Jurkat cells, poly(I:C) and NO donors induced apoptosis as well as HMGB1 release. Together, these results indicate that HMGB1 release from macrophages is correlated with the occurrence of apoptosis and suggest that these processes reflect common mechanisms and can occur concomitantly.

Duke Scholars

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

May 15, 2007

Volume

178

Issue

10

Start / End Page

6495 / 6503

Location

United States

Related Subject Headings

  • Toll-Like Receptors
  • Protein Transport
  • Poly I-C
  • Oligodeoxyribonucleotides
  • Mice, Inbred BALB C
  • Mice
  • Macrophages, Peritoneal
  • Macrophage Activation
  • Lipopolysaccharides
  • Jurkat Cells
 

Citation

APA
Chicago
ICMJE
MLA
NLM

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

May 15, 2007

Volume

178

Issue

10

Start / End Page

6495 / 6503

Location

United States

Related Subject Headings

  • Toll-Like Receptors
  • Protein Transport
  • Poly I-C
  • Oligodeoxyribonucleotides
  • Mice, Inbred BALB C
  • Mice
  • Macrophages, Peritoneal
  • Macrophage Activation
  • Lipopolysaccharides
  • Jurkat Cells