title: Effects of downregulation of aquaporin1 by peptidoglycan and lipopolysaccharide via MAPK pathways in MeT-5A cells.
abstract: This study was designed to investigate the signaling pathway involved in aquaporin1 (AQP1) expression caused by peptidoglycan (PGN) from Staphylococcus aureus and lipopolysaccharide (LPS) in human pleural mesothelial cell lines (MeT-5A) in vitro. RT-PCR, immunoblot analysis, and immunofluorescence assay were used to determine the relative mRNA and protein levels of AQP1 caused by PGN and LPS in MeT-5A cells. Activation of MAPKs by PGN and LPS was reflected by detecting the phosphorylation constituents of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 using immunoblot. MAPKs inhibitors were used to determine the effects of PGN- and LPS-induced AQP1 expression by immunoblot. AQP1 transcription and protein expression were decreased by PGN and LPS in dose- and time-dependent manners in MeT-5A cells. Both PGN and LPS activated p38/ERK/JNK pathways in MeT-5A cells. Furthermore, downregulation of AQP1 expression by LPS was blocked by SB203580, SP600125, and PD98059, which are inhibitors of p38, JNK, and ERK1/2, respectively. In contrast, downregulation of AQP1 expression by PGN was blocked only by SB203580, not by SP600125 or PD98059, underlying the importance of p38 MAPK in the downregulation of AQP1 expression by PGN in MeT-5A cells. AQP1 expression was decreased by both PGN and LPS in dose- and time-dependent manners in MeT-5A cells. AQP1 expression was down-regulated by PGN via p38 MAPK pathway, while AQP1 expression was down-regulated by LPS via p38/JNK/ERK pathways.
authors.affiliation: Department of Internal Medicine of Respiratory Disease, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Liu
authors.forename: Canmao
authors.initials: C
authors.lastname: Xie
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D051398:Aquaporin 1 / Q000037:antagonists & inhibitors*; D002460:Cell Line; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008070:Lipopolysaccharides; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010457:Peptidoglycan; D011725:Pyridines / Q000494:pharmacology; D013211:Staphylococcus aureus
chemical_list: D000873:Anthracenes; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D011725:Pyridines; D051398:Aquaporin 1; C432165:pyrazolanthrone; D020928:Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one