title: [Effect of MAPK/NF-kappaB signaling pathway on extracellular release of HMGB1 induced by hypoxia in laryngeal Hep-2 carcinoma cells].
abstract: OBJECTIVE
  To investigate the extracellular release of high mobility group box 1 (HMGB1) in laryngeal Hep-2 carcinoma cells induced by hypoxia and its possible mechanism.
  
  
  METHODS
  The changes of HMGB1 concentration in the culture medium as well as HMGB1 protein and mRNA expression in Hep-2 cells were investigated after the cells were cultured with 1% O2 for different durations. Inhibitory effects of MAPK pathway inhibitors (PD98059. SP600125, and SB202190) and nuclear NF-kappaB pathway inhibitor (PDTC) with various concentrations on extracellular HMGB1 release were observed in hypoxia-induced Hep-2 cells. The HMGB1 concentration and HMGB1 protein expression were measured by enzyme-linked immunosorbent assay (ELISA) and western blot, respectively. The HMGB1 mRNA expression was determined by real-time quantitative PCR(RT-PCR).
  
  
  RESULTS
  The HMGB1 concentration in the culture medium and the HMGB1 protein expression in Hep-2 cells increased after the cells were subjected to hypoxia culture for 12 h in a time-dependent manner. The level of HMGB1 mRNA expression in Hep-2 cells increased after the cells were induced by hypoxia for 6h PD98059 and SP600125 with 20 micromol/ L and PDTC with 50 mg/L partly inhibited extracellular release of HMGB1 in hypoxia-cultured Hcp-2 cells.
  
  
  CONCLUSIONS
  Hypoxia induces laryngeal carcinoma cells to release HMGH1. which may be related to MAPK/NF-kappaB signaling pathway.
authors.affiliation: Department of Medical Laboratory, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, 214023, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Otolaryngology, Wuxi People's Hospital Affiliated to Nanjing Medical University.
authors.forename: Xiabing
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Medical Laboratory, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, 214023, China
authors.forename: Falong
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Medical Laboratory, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, 214023, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Han
authors.affiliation: Department of Otolaryngology, Wuxi People's Hospital Affiliated to Nanjing Medical University.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Medical Laboratory, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, 214023, China.
authors.forename: Guoqian
authors.initials: G
authors.lastname: Chen
mesh_terms: D000873:Anthracenes; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D005419:Flavonoids; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011759:Pyrrolidines; D012333:RNA, Messenger / Q000235:genetics; D013859:Thiocarbamates
chemical_list: D000873:Anthracenes; D005419:Flavonoids; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D007093:Imidazoles; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; C432165:pyrazolanthrone; C020972:pyrrolidine dithiocarbamic acid; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one