title: Pneumocystis cell wall beta-glucan stimulates calcium-dependent signaling of IL-8 secretion by human airway epithelial cells.
abstract: BACKGROUND
  Respiratory failure secondary to alveolar inflammation during Pneumocystis pneumonia is a major cause of death in immunocompromised patients. Neutrophil infiltration in the lung of patients with Pneumocystis infection predicts severity of the infection and death. Several previous studies indicate that airway epithelial cells release the neutrophil chemoattractant proteins, MIP-2 (rodents) and IL-8 (humans), in response to Pneumocystis and purified Pneumocystis cell wall beta-glucans (PCBG) through the NF-kappaB-dependent pathway. However, little is known about the molecular mechanisms that are involved in the activation of airway epithelium cells by PCBG resulting in the secretion of IL-8.
  
  
  METHODS
  To address this, we have studied the activation of different calcium-dependent mitogen-activated protein kinases (MAPKs) in 1HAEo- cells, a human airway epithelial cell line.
  
  
  RESULTS
  Our data provide evidence that PCBG induces phosphorylation of the MAPKs, ERK, and p38, the activation of NF-kappaB and the subsequently secretion of IL-8 in a calcium-dependent manner. Further, we evaluated the role of glycosphingolipids as possible receptors for beta-glucans in human airway epithelial cells. Preincubation of the cells with D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) a potent inhibitor of the glycosphingolipids synthesis, prior to PCBG stimulation, significantly decreased IL-8 production.
  
  
  CONCLUSIONS
  These data indicate that PCBG activates calcium dependent MAPK signaling resulting in the release of IL-8 in a process that requires glycosphingolipid for optimal signaling.
authors.affiliation: Thoracic Diseases Research Unit, Division of Pulmonary Critical Care and Internal Medicine, Department of Medicine Mayo Clinic and Foundation, Rochester, Minnesota, 55905, USA.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Carmona
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lamont
authors.forename: Ailing
authors.initials: A
authors.lastname: Xue
authors.forename: Mark
authors.initials: M
authors.lastname: Wylam
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Limper
mesh_terms: D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D002473:Cell Wall / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006028:Glycosphingolipids / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D045363:Pneumocystis carinii / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014162:Transfection; D047071:beta-Glucans / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C508606:CXCL8 protein, human; D004791:Enzyme Inhibitors; D006028:Glycosphingolipids; D016209:Interleukin-8; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D047071:beta-Glucans; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases