Optometry Research Today is a free monthly online journal that collates and summarizes the latest research about Optometry, including details on myopia, optometric practice, therapy. | ||||||||
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Hydrogen peroxide stimulates macrophages and monocytes to actively release HMGB1.Tang D, Shi Y, Kang R, Li T, Xiao W, Wang H, Xiao X *Laboratory of Shock, Department of Pathophysiology, Xiangya School of Medicine, and Departments of Pediatrics and Rheumatology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; College of Optometry, University of Houston, Houston, Texas, USA; and ||Department of Emergency Medicine, North Shore University Hospital, New York University School of Medicine, Manhasset, New York, USA. 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-alpha, IL-1, and IFN-gamma) 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, H2O2 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, CRM1, in macrophage/monocyte cultures. Inhibitors specific for the JNK (SP600125) and MEK (PD98059), but not p38 MAPK (SB203580), abrogated H2O2-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. Published 30 November 2006 in J Leukoc Biol.
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