TY - JOUR
T1 - Hydrogen peroxide stimulates macrophages and monocytes to actively release HMGB1
AU - Tang, Daolin
AU - Shi, Yongzhong
AU - Kang, Rui
AU - Li, Tong
AU - Xiao, Weimin
AU - Wang, Haichao
AU - Xiao, Xianzhong
PY - 2007/3/1
Y1 - 2007/3/1
N2 - 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.
AB - 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.
KW - CRm1
KW - Cytokine
KW - MAPK
KW - Nuclear protein
KW - Oxidative stress
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U2 - 10.1189/jlb.0806540
DO - 10.1189/jlb.0806540
M3 - Article
C2 - 17135572
AN - SCOPUS:33847775295
SN - 0741-5400
VL - 81
SP - 741
EP - 747
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 3
ER -