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The activation of HMGB1 as a progression factor on inflammation response in normal human bronchial epithelial cells through RAGE/JNK/NF-κB pathway

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Abstract

Extracellular high-mobility group box-1 (HMGB-1) has been implicated in the inflammation response leading to the precancerous lesions of non-small cell lung cancer (NSCLC). However, the role of HMGB-1 in the inflammation response in normal human bronchial epithelial (NHBE) cells and its underlying mechanisms were still not fully understood. In this study, the inflammation response in NHBE cells was stimulated by 2.5, 5, and 10 μg/ml HMGB-1. However, the receptor for advanced glycation end products (RAGE) blocker RAGE-Ab (5 μg/ml) or 10 μM c-Jun N-terminal kinases (JNK) inhibitor SP600125 could inhibit HMGB1-induced the release of inflammation cytokines including TNF-α, IL-8, IL-10, and MCP-1 in a dose-dependent manner. Furthermore, HMGB1-induced RAGE protein expression, JNK and NF-κB activation were attenuated by the pretreatment with RAGE-Ab or JNK inhibitor SP600125 in Western blot analysis. Our data indicated that HMGB-1 induced inflammation response in NHBE cells through activating RAGE/JNK/NF-κB pathway. HMGB-1 could act as a therapeutic target for inflammation leading NHBE cells to the precancerous lesions of NSCLC.

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Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (No. 81172503).

Conflict of interest

We declare that there is no conflict of interest. No author has any financial interest or conflict of interest involved with this study.

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Authors and Affiliations

  1. Department of Radiation Oncology, The First People’s Hospital of Xuzhou, 19#, Zhongshan North Road, Xuzhou, 221002, Jiangsu, People’s Republic of China

    Xiaojin Wu

  2. Department of Pharmacy, Xuzhou Medical College, Xuzhou, 221002, People’s Republic of China

    Yanyan Mi & Ankang Hu

  3. Department of Neurosurgery, The First People’s Hospital of Xuzhou, Xuzhou, 221002, People’s Republic of China

    Hui Yang & Qingguo Zhang

  4. Department of Respiratory, The First People’s Hospital of Xuzhou, Xuzhou, 221002, People’s Republic of China

    Chunli Shang

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  1. Xiaojin Wu
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  2. Yanyan Mi
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  3. Hui Yang
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  4. Ankang Hu
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  5. Qingguo Zhang
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Correspondence to Xiaojin Wu.

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Wu, X., Mi, Y., Yang, H. et al. The activation of HMGB1 as a progression factor on inflammation response in normal human bronchial epithelial cells through RAGE/JNK/NF-κB pathway. Mol Cell Biochem 380, 249–257 (2013). https://doi.org/10.1007/s11010-013-1680-0

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  • DOI: https://doi.org/10.1007/s11010-013-1680-0

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