caa a22 4500 606234470 CHVBK 20210128101237.0 cr unu---uuuuu 210128e20150701xx s 000 0 eng 10.1007/s11010-015-2396-0 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2396-0 HMGB1 binding to receptor for advanced glycation end products enhances inflammatory responses of human bronchial epithelial cells by activating p38 MAPK and ERK1/2 [Elektronische Daten] [Yue Liang, Changchun Hou, Jinliang Kong, Hanchun Wen, Xiaowen Zheng, Lihong Wu, Hong Huang, Yiqiang Chen] The proinflammatory factor high mobility group box protein 1 (HMGB1) has been implicated as an important mediator of many chronic inflammatory diseases, including asthma. Human bronchial epithelial cells (HBECs) play a central role in the pathogenesis of asthma. However, the effects of HMGB1 on HBECs and the underlying mechanisms remain unknown. Here, we investigated receptor expression and proinflammatory cytokine production by primary cultures of HBECs stimulated by HMGB1. We then examined the effects of specific receptor blockade and inhibition of p38 MAPK, ERK1/2, or PI3-K on HMGB1-induced expression of proinflammatory cytokines. HMGB1 increased the expression and secretion of TNF-α, TSLP, MMP-9, and VEGF in a dose- and time-dependent manner. HMGB1 also induced elevated expression of RAGE protein. Secretion of TNF-α, VEGF, MMP-9, and TSLP was significantly decreased by RAGE blockade and p38 MAPK pathway inhibition, while a less pronounced effect was mediated by ERK1/2 inhibition. These observations suggest that HMGB1 binds RAGE and promotes activities of p38 MAPK and ERK1/2 pathways in HBECs. This then enhances the expression of TNF-α, VEGF, MMP-9, and TSLP, which are the important inflammatory factors in asthma. These results demonstrate that HMGB1 enhances the inflammatory responses of HBECs, which are involved in the modulation of inflammatory processes in asthma. Springer Science+Business Media New York, 2015 High mobility group box protein 1 (HMGB1) nationallicence Human bronchial epithelial cells (HBECs) nationallicence Receptor nationallicence Signal transduction nationallicence Liang Yue The Research Department of Respiration Diseases, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China aut Hou Changchun The Research Department of Respiration Diseases, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China aut Kong Jinliang The Research Department of Respiration Diseases, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China aut Wen Hanchun The Research Department of Respiration Diseases, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China aut Zheng Xiaowen The Research Department of Respiration Diseases, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China aut Wu Lihong The Research Department of Respiration Diseases, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China aut Huang Hong The Research Department of Respiration Diseases, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China aut Chen Yiqiang The Research Department of Respiration Diseases, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 405/1-2(2015-07-01), 63-71 0300-8177 405:1-2<63 2015 405 11010 https://doi.org/10.1007/s11010-015-2396-0 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2396-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Liang Yue The Research Department of Respiration Diseases, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China aut NATIONALLICENCE 700 1- Hou Changchun The Research Department of Respiration Diseases, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China aut NATIONALLICENCE 700 1- Kong Jinliang The Research Department of Respiration Diseases, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China aut NATIONALLICENCE 700 1- Wen Hanchun The Research Department of Respiration Diseases, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China aut NATIONALLICENCE 700 1- Zheng Xiaowen The Research Department of Respiration Diseases, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China aut NATIONALLICENCE 700 1- Wu Lihong The Research Department of Respiration Diseases, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China aut NATIONALLICENCE 700 1- Huang Hong The Research Department of Respiration Diseases, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China aut NATIONALLICENCE 700 1- Chen Yiqiang The Research Department of Respiration Diseases, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 405/1-2(2015-07-01), 63-71 0300-8177 405:1-2<63 2015 405 11010