Amelioration of compound 4,4¡ä-diphenylmethane-bis(methyl)carbamate on high mobility group box1-mediated inflammation and oxidant stress responses in human umbilical vein endothelial cells via RAGE/ERK1/2/NF-¦ÊB pathway

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• 作者：Liang Feng^a ; ¹ ; ^{wenmoxiushi@163.com} ; Maomao Zhu^a ; ¹ ; Minghua Zhang^a ; Xiaobin Jia^a ; Xudong Cheng^b ; ^d ; Shumin Ding^a ; ^d ; Quan Zhu^b ; ^c ;
• 关键词：AGEs ; advanced glycation end products ; HMGB1 ; high mobility group box1 ; CM1 ; 4 ; 4&prime ; -diphenylmethane-bis(methyl) carbamate ; HUVECs ; human umbilical vein endothelial cells ; ICAM-1 ; intercellular adhesion molecule-1 ; TGF-¦Â1 ; transforming growth factor-b
• 刊名：International Immunopharmacology
• 出版年：2013
• 出版时间：February, 2013
• 年：2013
• 卷：15
• 期：2
• 页码：206-216
• 全文大小：2526 K

文摘

High mobility group box-1 (HMGB1), a secreted nuclear protein, acts as an inflammatory mediator and has been implicated in pathophysiological damage of diabetic vascular complications. A compound 4,4¡ä-diphenylmethane-bis(methyl) carbamate (CM1) has a protective activity on advanced glycation end products (AGEs)-induced endothelial dysfunction in our previous study. The aim of this study was to investigate whether CM1 could attenuate HMGB1-induced endothelial dysfunction in human umbilical vein endothelial cells (HUVECs), and also elucidate the possible underlying mechanism. The pre-treatment of CM1 (10^? 9 M) could inhibit significantly the migration of macrophages in co-incubation with HUVECs system. HMGB1 stimulated intercellular adhesion molecule-1 (ICAM-1), transforming growth factor-beta1 (TGF-¦Â1) and receptor for advanced glycation end products (RAGE) protein expression in HUVECs, which were inhibited by pretreatment with CM1. Furthermore, it also reduced significantly reactive oxygen species (ROS) generation and inflammatory cytokine interleukin-6 (IL-6) level in co-incubation system. Immunofluorescence and Western blotting assays showed that CM1 could attenuate HMGB1-induced intracellular ERK1/2 and NF-kB activation in HUVECs. Our findings indicated that CM1 attenuated HMGB1-mediated endothelial activation by ameliorating inflammation and oxidant stress responses via RAGE/ERK1/2/NF-¦ÊB pathway.