title: The activation of HMGB1 as a progression factor on inflammation response in normal human bronchial epithelial cells through RAGE/JNK/NF-κB pathway.
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.
authors.affiliation: Department of Radiation Oncology, The First People's Hospital of Xuzhou, 19#, Zhongshan North Road, Xuzhou 221002, Jiangsu, People's Republic of China. wuxiaojin2008@163.com
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Wu
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Mi
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Ankang
authors.initials: A
authors.lastname: Hu
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Zhang
authors.forename: Chunli
authors.initials: C
authors.lastname: Shang
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D024243:HMGB1 Protein / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000873:Anthracenes; D018932:Chemokine CCL2; D016207:Cytokines; D024243:HMGB1 Protein; D018836:Inflammation Mediators; D016209:Interleukin-8; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases