title: Nasal challenge with LPS stimulates the release of macrophage inflammatory protein 1alpha.
abstract: BACKGROUND
  Bacterial infections can cause a variety of airway diseases. Toll-like receptors (TLRs) directly respond to the presence of microbes and partake in the innate immune defense. TLR4 is activated by lipopolysaccharide (LPS), and has been detected in sinonasal tissue, epithelial cells and various inflammatory cells. Macrophage inflammatory protein 1alpha (MIP-1alpha) is a chemokine released during the inflammatory process. The present study investigated the potential role and regulation of MIP-1alpha in LPS-induced nasal inflammation.
  
  
  METHODS
  Thirty-two healthy individuals were intranasally challenged with LPS or vehicle. Nasal lavage was performed, followed by a nasal biopsy. Inflammatory cells were counted, MIP-1alpha levels analyzed and expression of MIP-1alpha mRNA in biopsies quantified. Neutrophils isolated from peripheral blood were treated with LPS and effects on MIP-1alpha release, cell survival, and the involved signal pathways, were investigated.
  
  
  RESULTS
  LPS challenge caused an increase of MIP-1alpha in nasal lavage. No corresponding change in mRNA expression was seen in nasal biopsies, suggesting the increase was not due to epithelial synthesis. Neutrophil numbers increased after LPS provocation. Treatment of isolated neutrophils with LPS delayed neutrophil apoptosis and resulted in a time- and concentration-dependent release of MIP-1alpha, which was reduced by inhibitors of transcription and of nuclear factor (NF)-kappaB, protein kinase C (PKC) and p38 MAPK pathways.
  
  
  CONCLUSIONS
  Nasal LPS challenge results in release of MIP-1alpha. The release most likely originates from recruited neutrophils, via NF-kappaB-, PKC- and p38 MAPK-dependent pathways. LPS stimulation delayed neutrophil apoptosis. MIP-1alpha may constitute an important mediator in neutrophilic airway disease.
authors.affiliation: Division of ENT Diseases Huddinge, Karolinska Institute, Stockholm, Sweden.
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Ekman
authors.forename: Mattias
authors.initials: M
authors.lastname: Fransson
authors.forename: Camilla
authors.initials: C
authors.lastname: Rydberg
authors.forename: Mikael
authors.initials: M
authors.lastname: Adner
authors.forename: Lars-Olaf
authors.initials: LO
authors.lastname: Cardell
mesh_terms: D000328:Adult; D017304:Annexin A5 / Q000276:immunology / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D054405:Chemokine CCL3 / Q000276:immunology / Q000378:metabolism*; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D017817:Nasal Lavage Fluid / Q000276:immunology; D009299:Nasal Provocation Tests; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000276:immunology / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology
chemical_list: D017304:Annexin A5; D000893:Anti-Inflammatory Agents; C515429:CCL3 protein, human; D054405:Chemokine CCL3; D008070:Lipopolysaccharides; D047428:Protein Kinase Inhibitors; D011500:Protein Synthesis Inhibitors; D003609:Dactinomycin; D003907:Dexamethasone; D011494:Protein Kinases