title: Regulation of secretory leukocyte proteinase inhibitor (SLPI) production by human bronchial epithelial cells: increase of cell-associated SLPI by neutrophil elastase.
abstract: BACKGROUND
  To protect against the extracellular activity of serine proteinases, the lung is equipped with serine proteinase inhibitors including secretory leukocyte proteinase inhibitor (SLPI) and elafin. Both SLPI and elafin are locally produced by airway epithelial cells, but the mechanisms that regulate the expression of these proteinase inhibitors are relatively unknown. Previous studies using airway epithelial cell lines indicated that neutrophil elastase (NE) increases SLPI mRNA transcripts while decreasing SLPI protein release. Similar results were observed for elafin. The aim of the present study was to investigate the effect of NE on SLPI and elafin synthesis in cultures of human primary bronchial epithelial cells (PBEC).
  
  
  METHODS
  Subcultures of human PBEC were incubated with NE, followed by preparation of cell-free supernatants and cellular lysates and determination of SLPI and elafin protein levels by enzyme-linked immunoadsorbent assay. The effect of NE on SLPI mRNA transcripts was determined by Northern blot analysis.
  
  
  RESULTS
  The results showed that NE increased SLPI mRNA expression while decreasing SLPI protein release. This NE-induced decrease was associated with an increase in cell-associated SLPI, providing an explanation for the apparent paradox of increased SLPI mRNA transcripts and decreased SLPI protein levels present in supernatants. In addition, NE had a stimulatory effect on the release of elafin by airway epithelial cells, whereas no increase in cell-associated elafin was observed.
  
  
  CONCLUSIONS
  The results from the present study indicate that NE may play a role in the regulation of the antiproteinase screen in the lung and the formation of a protective surface at the epithelial site.
authors.affiliation: Department of Pulmonology, Leiden University Medical Center, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: van Wetering
authors.forename: A C
authors.initials: AC
authors.lastname: van der Linden
authors.forename: M A
authors.initials: MA
authors.lastname: van Sterkenburg
authors.forename: K F
authors.initials: KF
authors.lastname: Rabe
authors.forename: J
authors.initials: J
authors.lastname: Schalkwijk
authors.forename: P S
authors.initials: PS
authors.lastname: Hiemstra
mesh_terms: D015152:Blotting, Northern; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism*; D056649:Cathepsin G; D002403:Cathepsins / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D019272:Leukocyte Elastase / Q000494:pharmacology*; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D053481:Secretory Leukocyte Peptidase Inhibitor; D012697:Serine Endopeptidases; D015842:Serine Proteinase Inhibitors / Q000235:genetics / Q000378:metabolism*; D000515:alpha 1-Antitrypsin / Q000494:pharmacology
chemical_list: D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D012333:RNA, Messenger; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D019272:Leukocyte Elastase