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Effect of high mobility group box-1 protein on apoptosis of peritoneal macrophages

Xiao-Mei Zhu1, Yong-Ming Yao, Hua-Ping Liang

  • 1Department of Microbiology and Immunology, Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, People's Republic of China.

Archives of Biochemistry and Biophysics
|October 6, 2009
PubMed

Insights

High mobility group box-1 protein (HMGB1) triggers macrophage apoptosis in a dose- and time-dependent manner. This process involves receptor for advanced glycation end products (RAGE) and caspase-3 activation, with decreased NF-kappaB/p65 activity.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • High mobility group box-1 protein (HMGB1) is a pro-inflammatory cytokine.
  • Macrophage apoptosis plays a role in various inflammatory diseases.

Purpose of the Study:

  • To investigate the effects of HMGB1 on macrophage apoptosis.
  • To elucidate the molecular mechanisms underlying HMGB1-induced macrophage apoptosis.

Main Methods:

  • Macrophage cultures were treated with varying concentrations and durations of HMGB1.
  • Receptor for advanced glycation end products (RAGE) expression, caspase-3 activation, and NF-kappaB/p65 activity were assessed.
  • Inhibitors of RAGE and caspase-3 were used to evaluate their role in apoptosis.

Main Results:

  • HMGB1 induced apoptosis in macrophages in a dose- and time-dependent manner, peaking at 24 hours.
  • HMGB1 treatment increased RAGE expression and caspase-3 activation.
  • Blocking RAGE and caspase-3 significantly reduced HMGB1-induced apoptosis.
  • NF-kappaB/p65 activity was decreased following HMGB1 treatment.

Conclusions:

  • HMGB1 induces macrophage apoptosis through RAGE and caspase-3 activation.
  • Inhibition of NF-kappaB signaling pathways may contribute to HMGB1-induced macrophage apoptosis.
  • These findings provide insights into the role of HMGB1 in inflammatory processes involving macrophages.

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