title: Protein Phosphatase 2A in Lipopolysaccharide-Induced Cyclooxygenase-2 Expression in Murine Lymphatic Endothelial Cells.
abstract: The lymphatic endothelium plays an important role in the maintenance of tissue fluid homeostasis. It also participates in the pathogenesis of several inflammatory diseases. However, little is known about the underlying mechanisms by which lymphatic endothelial cell responds to inflammatory stimuli. In this study, we explored the mechanisms by which lipopolysaccharide (LPS) induces cyclooxygenase (COX)-2 expression in murine lymphatic endothelial cells (SV-LECs). LPS caused increases in cox-2 mRNA and protein levels, as well as in COX-2 promoter luciferase activity in SV-LECs. These actions were associated with protein phosphatase 2A (PP2A), apoptosis signal-regulating kinase 1 (ASK1), JNK1/2 and p38MAPK activation, and NF-κB subunit p65 and C/EBPβ phosphorylation. PP2A-ASK1 signaling blockade reduced LPS-induced JNK1/2, p38MAPK, p65 and C/EBPβ phosphorylation. Transfection with PP2A siRNA reduced LPS's effects on p65 and C/EBPβ binding to the COX-2 promoter region. Transfected with the NF-κB or C/EBPβ site deletion of COX-2 reporter construct also abrogated LPS's enhancing effect on COX-2 promoter luciferase activity in SV-LECs. Taken together, the induction of COX-2 in SV-LECs exposed to LPS may involve PP2A-ASK1-JNK and/or p38MAPK-NF-κB and/or C/EBPβ cascade.
authors: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors: Yu-Fan
authors: YF
authors: Chuang
authors: Department of Microbiology and Immunology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors: Mei-Chieh
authors: MC
authors: Chen
authors: Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors: Shiu-Wen
authors: SW
authors: Huang
authors: Division of General Surgery, Department of Surgery, Landseed Hospital, Taoyuan, Taiwan.
authors: Ya-Fen
authors: YF
authors: Hsu
authors: Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors: George
authors: G
authors: Ou
authors: Department of Internal Medicine, Yuan's General Hospital, Kaohsiung, Taiwan.
authors: Yu-Jou
authors: YJ
authors: Tsai
authors: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors: Ming-Jen
authors: MJ
authors: Hsu
mesh_terms: D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; D054648:Protein Phosphatase 2