title: Peptidoglycan from Staphylococcus aureus increases MUC5AC gene expression via RSK1-CREB pathway in human airway epithelial cells.
abstract: Respiratory tract exposure to viruses, air pollutants, or bacterial pathogens can lead to pulmonary diseases. The molecular mechanism of mucous overproduction increased by these pathogens provides the knowledge for developing new therapeutic strategies. There is established in vitro data demonstrating that the overexpression of MUC5AC is induced by peptidoglycan (PGN) derived from Staphylococcus aureus. However, the mechanisms by which PGN activates MUC5AC gene expression in the airway remain unclear. The aim of this study was to identify the mechanism of PGN-induced MUC5AC gene expression. We found that PGN could induce MUC5AC gene expressions in a time- and dose-dependent manner. Moreover, activations of ERK1/2 and JNK increased after treatment of cells with PGN, whereas phosporylation of p38 was undetected. Of these MAPKs, pharmacologic inhibition of ERK1/2 decreased PGN-induced MUC5AC gene expression. In addition, we checked the activation of p90 ribosomal S6 kinase 1 (RSK1) as a downstream signaling target of ERK1/2 in PGN signaling. The activation of RSK1 was prevented by pretreatment with PD98059. We also found that RSK1 mediated the PGN-induced phosphorylation of cAMP response element-binding protein (CREB) and the transcription of MUC5AC. Furthermore, the cAMP-response element (CRE) in the MUC5AC promoter appears to be important for PGN-induced MUC5AC gene expression in NCI-H292 cells.
authors: Department of Physiology, Kosin University College of Medicine, Busan 602-703, Korea.
authors: Young Ok
authors: YO
authors: Kim
authors: Min Jung
authors: MJ
authors: Jung
authors: Jang Kyu
authors: JK
authors: Choi
authors: Do Whan
authors: do W
authors: Ahn
authors: Kyoung Seob
authors: KS
authors: Song
mesh_terms: D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology; D055272:Mucin-6 / Q000235:genetics / Q000378:metabolism*; D010457:Peptidoglycan / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000037:antagonists & inhibitors; D013203:Staphylococcal Infections / Q000235:genetics / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000276:immunology* / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D005419:Flavonoids; C524734:MUC6 protein, human; D055272:Mucin-6; D010457:Peptidoglycan; D000242:Cyclic AMP; C069329:RPS6KA1 protein, human; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one