Effect of high mobility group box-1 protein on apoptosis of peritoneal macrophages.
The present study was performed to clarify the effects of high mobility group box-1 protein (HMGB1), a recently described late-acting pro-inflammatory cytokine, on apoptosis of macrophages. Treatment with HMGB1 (0.01, 0.1, 1, 10 microg/ml for 24 h, or 10 microg/ml for 6, 12, 24, 48 h) resulted in a dose- and time-dependent induction of apoptosis in mice macrophages, peaked at 24 h after 10 microg/ml HMGB1 stimulation. HMGB1 treatment enhanced the receptor for advanced glycation end products (RAGE) expression and caspase-3 activation in macrophages. Blockage of RAGE and caspase-3 activation could significantly reduce apoptosis of macrophages induced by HMGB1. The activity of NF-kappaB/p65 in macrophages was decreased after HMGB1 treatment. These results suggested that HMGB1-induced apoptosis of macrophages in a dose- and time-dependent manner. RAGE, together with caspase-3 activation and inhibition of NF-kappaB signaling pathways, might be involved in the pathogenesis of macrophage apoptosis induced by HMGB1.
Department of Microbiology and Immunology, Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, People's Republic of China.
Xiao-Mei
XM
Zhu
Yong-Ming
YM
Yao
Hua-Ping
HP
Liang
Feng
F
Liu
Ning
N
Dong
Yan
Y
Yu
Zhi-Yong
ZY
Sheng
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D017737:Macrophages, Peritoneal / Q000166:cytology* / Q000201:enzymology / Q000276:immunology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D052002:NF-kappa B p50 Subunit / Q000037:antagonists & inhibitors / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
D048868:Adaptor Proteins, Signal Transducing; D061945:Caspase Inhibitors; D024243:HMGB1 Protein; D052002:NF-kappa B p50 Subunit; D011994:Recombinant Proteins; C073701:Nfkb1 protein, mouse; C498977:Mok protein, mouse; D020928:Mitogen-Activated Protein Kinases; C505409:Casp3 protein, mouse; D053148:Caspase 3