title: Glucocorticoids can affect Pseudomonas aeruginosa (ATCC 27853) internalization and intracellular calcium concentration in cystic fibrosis bronchial epithelial cells.
abstract: OBJECTIVE
  Glucocorticoids (GCs) are anti-inflammatory agents, but their use in cystic fibrosis (CF) is controversial. In CF, the early colonization with Pseudomonas aeruginosa is mainly due to nonmucoid strains that can internalize, and induce apoptosis in the epithelial cells. Uptake of P. aeruginosa by the epithelial cells and subsequent apoptosis may prevent colonization of P. aeruginosa in CF airways. In the airway epithelia, several other biological effects, including an anti-secretory role by decreasing intracellular Ca(2+) concentration have been described for this anti-inflammatory drug. However, the effects of GCs on the nonmucoid P. aeruginosa internalization and intracellular Ca(2+) in CF bronchial epithelial cells have not been evaluated.
  
  
  METHODS
  We used cultured human CF bronchial airway epithelial cell (CFBE) monolayers to determine P. aeruginosa internalization, apoptosis, and intracellular Ca(2+)concentration in CF bronchial epithelial cells. Cells were treated with IL-6, IL-8, dexamethasone, betamethasone, or budesonide.
  
  
  RESULTS
  GCs in co-treatments with IL-6 reversed the effect of IL-6 by decreasing the internalization of P. aeruginosa in the CFBE cells. GCs decreased the extent of apoptosis in CFBE cells infected with internalized P. aeruginosa, and increased the intracellular Ca(2+) concentration.
  
  
  CONCLUSIONS
  These findings suggest that if internalization of P. aeruginosa reduces infection, GC therapy would increase the risk of pulmonary infection by decreasing the internalization of P. aeruginosa in CF cells, but GCs may improve airway hydration by increasing the intracellular Ca(2+) concentration. Whether the benefits of GC treatment outweigh the negative effects is questionable, and further clinical studies need to be carried out.
authors.affiliation: a 1 School of Health and Medical Sciences , Örebro University , Örebro, Sweden.
authors.forename: Rashida
authors.initials: R
authors.lastname: Hussain
authors.affiliation: a 1 School of Health and Medical Sciences , Örebro University , Örebro, Sweden.
authors.forename: Rami
authors.initials: R
authors.lastname: Shahror
authors.affiliation: b 2 Stockholm CF-Center, Department of Pediatrics , Karolinska University Hospital Huddinge , Stockholm, Sweden.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Karpati
authors.affiliation: a 1 School of Health and Medical Sciences , Örebro University , Örebro, Sweden.
authors.forename: Godfried M
authors.initials: GM
authors.lastname: Roomans
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D019819:Budesonide / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000382:microbiology*; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D016209:Interleukin-8 / Q000494:pharmacology; D011552:Pseudomonas Infections; D011550:Pseudomonas aeruginosa / Q000187:drug effects*
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D015850:Interleukin-6; D016209:Interleukin-8; D019819:Budesonide; D003907:Dexamethasone; D002118:Calcium
keywords: Cystic fibrosis; Pseudomonas aeruginosa; glucocorticoids; internalization; intracellular Ca2+