HMGB1 activates nuclear factor-κB signaling by RAGE and increases the production of TNF-α in human umbilical vein endothelial cells
栾正刚1 马晓春1
中国医科大学附属第一医院重症医学科
Objective: We investigated the effects of HMGB1 on the activation of HUVECs and defined pathways activated by HMGB1.
Methods: The activation of HUVECs was studied regarding (i) the kinetics of TNF-α production in HUVECs, (ii) HMGB1-induced upregulation of receptor for RAGE, (iii) HMGB1-induced nuclear translocation of NF-κB in HUVECs.
Results: The HMGB1-induced activation of HUVECs was significantly inhibited by anti-RAGE monoclonal antibody and EP. Short-term prestimulation of HUVECs with HMGB1 caused a time-dependent increase in the secretion of TNF-α and expression of RAGE. Furthermore, HMGB1 stimulation resulted in nuclear translocation of transcription factor NF-κB. Pretreatment with anti-RAGE monoclonal antibody significantly decreased the amounts of TNF-α and inhibited the nuclear translocation of NF-κB.
Conclusions: Our data present a link between HMGB1and RAGE function of endothelial cells and demonstrate the pathway activated by HMGB1.
Methods: The activation of HUVECs was studied regarding (i) the kinetics of TNF-α production in HUVECs, (ii) HMGB1-induced upregulation of receptor for RAGE, (iii) HMGB1-induced nuclear translocation of NF-κB in HUVECs.
Results: The HMGB1-induced activation of HUVECs was significantly inhibited by anti-RAGE monoclonal antibody and EP. Short-term prestimulation of HUVECs with HMGB1 caused a time-dependent increase in the secretion of TNF-α and expression of RAGE. Furthermore, HMGB1 stimulation resulted in nuclear translocation of transcription factor NF-κB. Pretreatment with anti-RAGE monoclonal antibody significantly decreased the amounts of TNF-α and inhibited the nuclear translocation of NF-κB.
Conclusions: Our data present a link between HMGB1and RAGE function of endothelial cells and demonstrate the pathway activated by HMGB1.
