PMID- 25649981 OWN - NLM STAT- MEDLINE DCOM- 20160209 LR - 20190923 IS - 1738-8872 (Electronic) IS - 1017-7825 (Linking) VI - 25 IP - 5 DP - 2015 May TI - 15-Hydroxyeicosatetraenoic Acid Inhibits Phorbol-12-Myristate-13-Acetate-Induced MUC5AC Expression in NCI-H292 Respiratory Epithelial Cells. PG - 589-97 AB - 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-kappaB) into nuclear. Furthermore, 15-HETE enhanced transcriptional activity of peroxisome proliferator-activated receptor gamma (PPARgamma) as a PPARgamma agonist. This activity reduced phosphorylation of protein kinase B (PKappaB/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 PPARgamma/PTEN/ Akt signaling pathways in PMA-treated respiratory epithelial cells. FAU - Song, Yong-Seok AU - Song YS AD - Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea. FAU - Kim, Man Sub AU - Kim MS AD - Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea. FAU - Lee, Dong Hun AU - Lee DH AD - Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea. FAU - Oh, Doek-Kun AU - Oh DK AD - Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea. FAU - Yoon, Do-Young AU - Yoon DY AD - Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Korea (South) TA - J Microbiol Biotechnol JT - Journal of microbiology and biotechnology JID - 9431852 RN - 0 (MUC5AC protein, human) RN - 0 (Mucin 5AC) RN - 0 (Phorbol Esters) RN - 20839-06-9 (phorbol-12-myristate) RN - 97850-14-1 (15-hydroxy-5,8,11,13,17-eicosapentaenoic acid) RN - AAN7QOV9EA (Eicosapentaenoic Acid) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Cell Line, Tumor MH - Eicosapentaenoic Acid/*analogs & derivatives/pharmacology MH - Humans MH - MAP Kinase Signaling System/drug effects MH - Matrix Metalloproteinase 9/metabolism MH - Models, Biological MH - Mucin 5AC/genetics/*metabolism MH - Phorbol Esters/*pharmacology MH - Respiratory Mucosa/cytology/*drug effects EDAT- 2015/02/05 06:00 MHDA- 2016/02/10 06:00 CRDT- 2015/02/05 06:00 PHST- 2015/02/05 06:00 [entrez] PHST- 2015/02/05 06:00 [pubmed] PHST- 2016/02/10 06:00 [medline] AID - 10.4014/jmb.1501.01052 [pii] AID - 10.4014/jmb.1501.01052 [doi] PST - ppublish SO - J Microbiol Biotechnol. 2015 May;25(5):589-97. doi: 10.4014/jmb.1501.01052.