title: Lipopolysaccharide and platelet-activating factor stimulate expression of platelet-activating factor acetylhydrolase via distinct signaling pathways.
abstract: OBJECTIVE
  This study was designed to investigate and characterize the ability of platelet-activating factor (PAF) to induce the expression of platelet-activating factor acetylhydrolase (PAF-AH).
  
  
  METHODS
  Ribonuclease protection assays and quantitative real-time PCR were used to investigate the ability of lipopolysaccharide (LPS) and PAF to regulate PAF-AH mRNA expression in human monocyte-macrophage 6 (MM6) cells. Pharmacological inhibitors of mitogen activated protein kinases (MAPK) and PAF receptor antagonists were used to investigate the mechanism of regulation of PAF-AH.
  
  
  RESULTS
  PAF-AH mRNA levels were increased upon exposure to LPS or PAF in a dose-dependent manner. LPS elicited a more potent and rapid increase in PAF-AH expression than the PAF-stimulated response. However, when administered concomitantly, PAF augmented the LPS-stimulated response. LPS-stimulated PAF-AH expression was susceptible to partial inhibition by a p38 MAPK inhibitor and PAF receptor antagonists. PAF-induced up-regulation of PAF-AH levels was solely mediated via the PAF receptor and was p38 MAPK-independent.
  
  
  CONCLUSIONS
  The proinflammatory mediators, LPS and PAF, increased levels of PAF-AH mRNA via distinct signaling pathways.
authors: Department of Biomedical Sciences, University of Nevada Las Vegas School of Dental Medicine, 1001 Shadow Lane, Las Vegas, Nevada 89106, USA. Katherine.howard@unlv.edu
authors: Katherine M
authors: KM
authors: Howard
authors: Mohammed
authors: M
authors: Abdel-Al
authors: Marcia
authors: M
authors: Ditmyer
authors: Nipa
authors: N
authors: Patel
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics / Q000378:metabolism*; D001381:Azepines / Q000378:metabolism; D002460:Cell Line / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D014230:Triazoles / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D001381:Azepines; D004791:Enzyme Inhibitors; D007093:Imidazoles; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011725:Pyridines; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; C064509:BN 50739; C063964:bepafant; D048051:p38 Mitogen-Activated Protein Kinases; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C093642:SB 203580