title: 15-Hydroxyeicosatetraenoic Acid Inhibits Phorbol-12-Myristate-13-Acetate-Induced MUC5AC Expression in NCI-H292 Respiratory Epithelial Cells.
abstract: It has been reported that overexpression of MUC5AC induced by excessive inflammation leads to airway obstruction in respiratory diseases such as chronic obstructive pulmonary disease and asthma. 15-Hydroxyeicosatetraenoic acid (15-HETE) has been reported to have anti-inflammatory effects, but the role of 15-HETE in respiratory inflammation has not been determined. Therefore, the aim of this study was to investigate the effects of 15-HETE on MUC5AC expression and related pathways. In this study, phorbol-12-myristate-13-acetate (PMA) was used to stimulate NCI-H292 bronchial epithelial cells in order to examine the effects of 15-HETE. 15-HETE inhibited PMA-induced expression of MUC5AC mRNA and secretion of MUC5AC protein. Also, 15-HETE regulated matrix metallopeptidase 9 (MMP-9), mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated kinase (ERK). In addition, 15-HETE decreased translocation of specificity protein-1 (Sp-1) transcription factor and nuclear factor kappaB (NF-κB) into nuclear. Furthermore, 15-HETE enhanced transcriptional activity of peroxisome proliferator-activated receptor γ (PPARγ) as a PPARγ agonist. This activity reduced phosphorylation of protein kinase B (PΚB/Akt) by increasing the expression of phosphatase and tensin homolog (PTEN). In conclusion, 15-HETE regulated MUC5AC expression via modulating MMP-9, MEK/ERK/Sp-1 and PPARγ/PTEN/ Akt signaling pathways in PMA-treated respiratory epithelial cells.
authors: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Yong-Seok
authors: YS
authors: Song
authors: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Man Sub
authors: MS
authors: Kim
authors: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Dong Hun
authors: DH
authors: Lee
authors: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Doek-Kun
authors: DK
authors: Oh
authors: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Do-Young
authors: DY
authors: Yoon
mesh_terms: D045744:Cell Line, Tumor; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008954:Models, Biological; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology*; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects*
chemical_list: C524678:MUC5AC protein, human; D055271:Mucin 5AC; D010703:Phorbol Esters; C119222:phorbol-12-myristate; C059164:15-hydroxy-5,8,11,13,17-eicosapentaenoic acid; D015118:Eicosapentaenoic Acid; D020780:Matrix Metalloproteinase 9