Reduced Interleukin-8 Production by Cystic Fibrosis Airway Epithelial Cells

Details

• Personal Author:
  Aronoff SC ; Cuff C ; Massengale AD ; McClellan WT ; Quinn F ; Weissman, David N. ; Yankaskas J
• Description:
  The acquisition of Pseudomonas aeruginosa in the airways of patients with cystic fibrosis (CF) is the initial event leading to bronchiectasis and lung disease. Although the host factors that permit initial airway colonization are largely unknown, recent studies suggest that secretion of interleukin (IL)-8 by airway epithelia and local recruitment of neutrophils is the final pathway in a pulmonary cytokine network. To determine whether differences in cytokine production exist between normal and CF airway epithelia, secretion of immunoreactive IL-8 and IL-10 as well as specific messenger RNA (mRNA) abundance were compared in airway epithelia expressing normal and mutant CF transmembrane regulator. After induction with IL-1, a CF airway cell line engineered to express the wild-type CF gene (CFT1-LCFSN) secreted significantly more immunoreactive IL-8 than did its isogenic parent that expressed the mutant CF gene (CFT1) or an isogenic vector control line (CFT1-LC3). Further studies with the three related cell lines demonstrated that expression of CFT1-LCFSN was associated with a significant increase in uninduced secretion of immunoreactive IL-8 as well as a 10- to 20-fold increase in IL-8 mRNA abundance when compared with the isogenic lines expressing the mutant gene. IL-1 induction and intracellular accumulation of IL-8 appeared to be unaffected by CF genotype. These studies suggest that IL-8 secretion by CF airway epithelial cells is defective and may contribute to Pseudomonas persistence in the CF airway. Further studies are needed to confirm this difference in other cell lines and determine the linkage between IL-8 production and CF gene expression. [Description provided by NIOSH]
• Subjects:
  Communicable Diseases Fibrosis Lung Diseases Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  Airway-obstruction Infectious-diseases Lung-disease Lung-disorders Pulmonary-system-disorders
• ISSN:
  1044-1549
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  20
• Issue:
  5
• NIOSHTIC Number:
  nn:20000899
• Citation:
  Am J Respir Cell Mol Biol 1999 May; 20(5):1073-1080
• Contact Point Address:
  Stephen C. Aronoff, M.D., Dept. of Pediatrics, West Virginia University School of Medicine, P.O. Box 9214, Morgantown, WV 26506-9214
• Email:
  saronoff@wvu.edu
• Federal Fiscal Year:
  1999
• Peer Reviewed:
  True
• Source Full Name:
  American Journal of Respiratory Cell and Molecular Biology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9aeacea78aa3bdb16d19d6556b6d4f72f3e40a3dfd5bc9b64ae7455e327452043204b63a7229764869b041abed16186b08f6b97e393d6bdbc96ddd03bb83aa91
• Download URL:
  https://stacks.cdc.gov/view/cdc/198244/cdc_198244_DS1.pdf
• File Type:
  [PDF - 148.41 KB ]