title: High-mobility group box-1 protein induces mucin 8 expression through the activation of the JNK and PI3K/Akt signal pathways in human airway epithelial cells.
abstract: High-mobility group box-1 protein (HMGB1), which is produced by immune cells, was recently identified as a proinflammatory mediator in various inflammatory diseases. In this study, we investigated the effect of HMGB1 on the expression of mucin (MUC) genes in human airway epithelial cells. We showed that HMGB1 markedly increased MUC8 expression, and that the expression of other MUC genes was also regulated by HMGB1. HMGB1 activated the JNK and PI3K/Akt signaling pathways, and inhibitors of JNK and PI3K/Akt markedly inhibited HMGB1-induced MUC8 expression. Furthermore, HMGB1 increased the production of intracellular reactive oxygen species (ROS). However, the ROS scavengers Trolox and N-acetylcysteine (NAC) had no effect on MUC8 expression in HMGB1-treated NCI-H292 cells. Taken together, our results suggest that HMGB1 induces MUC8 expression in a JNK and PI3K/Akt signaling pathway-dependent manner but that HMGB1 acts in an ROS-independent manner.
authors.affiliation: Department of Otolaryngology, School of Medicine, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, Republic of Korea.
authors.forename: Dong Eun
authors.initials: DE
authors.lastname: Kim
authors.forename: Kyoung-jin
authors.initials: KJ
authors.lastname: Min
authors.forename: Jung Soo
authors.initials: JS
authors.lastname: Kim
authors.forename: Taeg Kyu
authors.initials: TK
authors.lastname: Kwon
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D002460:Cell Line; D002839:Chromans / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000096:biosynthesis; D009077:Mucins / Q000096:biosynthesis* / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D002839:Chromans; D016166:Free Radical Scavengers; D024243:HMGB1 Protein; C105059:MUC8 protein, human; D009077:Mucins; D017382:Reactive Oxygen Species; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048670:MAP Kinase Kinase 4; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D000111:Acetylcysteine