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HMGB1 binding to receptor for advanced glycation end products enhances inflammatory responses of human bronchial epithelial cells by activating p38 MAPK and ERK1/2

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Abstract

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.

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Acknowledgments

This study was supported by Scientific Research and Technological Development Program Project of Guangxi Province (10124001A-32), the young science foundation of Guangxi Medical University (GXMUSF201206), and Innovation Project of Guangxi Graduate Education (YCBZ2013014).

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    Authors and Affiliations

    1. The Research Department of Respiration Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China

      Yue Liang, Changchun Hou, Jinliang Kong, Hanchun Wen, Xiaowen Zheng, Lihong Wu, Hong Huang & Yiqiang Chen

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    1. Yue Liang
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    2. Changchun Hou
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    3. Jinliang Kong
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    4. Hanchun Wen
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    5. Xiaowen Zheng
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    7. Hong Huang
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    Correspondence to Yue Liang or Yiqiang Chen.

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    Yue Liang and Changchun Hou have contributed equally to this work.

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    Liang, Y., Hou, C., Kong, J. et al. HMGB1 binding to receptor for advanced glycation end products enhances inflammatory responses of human bronchial epithelial cells by activating p38 MAPK and ERK1/2. Mol Cell Biochem 405, 63–71 (2015). https://doi.org/10.1007/s11010-015-2396-0

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