Hydrogen peroxide stimulates macrophages and monocytes to actively release HMGB1

Daolin Tang, Yongzhong Shi, Rui Kang, Tong Li, Weimin Xiao, Haichao Wang, Xianzhong Xiao

Research output: Contribution to journalArticlepeer-review

260 Scopus citations


High mobility group box 1 (HMGB1) can be actively secreted by macrophages/monocytes in response to exogenous and endogenous inflammatory stimuli (such as bacterial endotoxin, TNF-α, IL-1, and IFN-γ) or passively released by necrotic cells and mediates innate and adaptive inflammatory responses to infection and injury. Here, we demonstrated that a reactive oxygen species, hydrogen peroxide (H2O2), induces active and passive HMGB1 release from macrophage and monocyte cultures in a time- and dose-dependent manner. At nontoxic doses (e.g., 0.0125-0.125 mM), H2O2 induced HMGB1 cytoplasmic translocation and active release within 3-24 h. At higher concentrations (e.g., 0.25 mM), however, H 2O2 exhibited cytotoxicity to macrophage and monocyte cell cultures and consequently, triggered active and passive HMGB1 release. In addition, H2O2 stimulated potential interaction of HMGB1 with a nuclear export factor, chromosome region maintenance (CRM1), in macrophage/monocyte cultures. Inhibitors specific for the JNK (SP600125) and MEK (PD98059), but not p38 MAPK (SB203580), abrogated H2O 2-induced, active HMGB1 release. Together, these data establish an important role for oxidative stress in inducing active HMGB1 release, potentially through a MAPK- and CRM1-dependent mechanism.

Original languageEnglish (US)
Pages (from-to)741-747
Number of pages7
JournalJournal of Leukocyte Biology
Issue number3
StatePublished - Mar 1 2007
Externally publishedYes


  • CRm1
  • Cytokine
  • MAPK
  • Nuclear protein
  • Oxidative stress

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology


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