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.
Zhu
Xiao-Mei
XM
Department of Microbiology and Immunology, Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, People's Republic of China.
Yao
Yong-Ming
YM
Liang
Hua-Ping
HP
Liu
Feng
F
Dong
Ning
N
Yu
Yan
Y
Sheng
Zhi-Yong
ZY
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