Release of interleukin-8, interleukin-6, and colony-stimulating factors by upper airway epithelial cells: implications for cystic fibrosis.
Cystic fibrosis (CF) is characterized by a dramatic neutrophil recruitment and repeated Pseudomonas infections in the lungs. To evaluate cytokine releasibility by airway epithelial cells in the context of CF, we studied primary nasal epithelial cells isolated from the upper airways and continuous epithelial cell lines from normal and CF subjects. Relatively low levels of interleukin (IL)-8, IL-6, and granulocyte/macrophage colony-stimulating factor (GM-CSF) were produced spontaneously by primary epithelial cells (< 50 pg/10(6) cells) and higher levels of colony-stimulating factor-1 (CSF-1) (1 to 2 ng/10(6) cells). Cells were stimulated with substances that are likely to be present in the inflamed lungs of CF patients-namely, the proinflammatory monokines IL-1 and tumor necrosis factor-alpha (TNF alpha) as well as neutrophil elastase and bacterial products from Pseudomonas (mucoid exopolysaccharide [MEP] and rhamnolipids). Both IL-1 and TNF alpha induced a dose-dependent release of IL-6 (5 to 10 ng/10(6) cells) and GM-CSF (2 to 3 ng/10(6) cells) by primary epithelial cells from eight normal volunteers. The TNF alpha/IL-1-stimulated GM-CSF release was blocked by the addition of 1 microM dexamethasone, whereas basal CSF-1 release was unaffected. Neutrophil elastase was a potent inducer of IL-8 and GM-CSF both in primary epithelial cells and in cell lines. Dexamethasone (1 microM) did not inhibit elastase-induced IL-8 release in either normal or CF epithelial cells. Rhamnolipids and MEP were found to stimulate the copious release of IL-8, GM-CSF, and IL-6 from epithelial cells, in a steroid-sensitive fashion.(ABSTRACT TRUNCATED AT 250 WORDS)
Bédard
M
M
Department of Anatomy and Cellular Biology, Faculty of Medicine, University of Sherbrooke, Quebec, Canada.
McClure
C D
CD
Schiller
N L
NL
Francoeur
C
C
Cantin
A
A
Denis
M
M
D000704:Analysis of Variance; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000276:immunology / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D009297:Nasal Mucosa / Q000166:cytology / Q000378:metabolism; D010641:Phenotype
C505032:CFTR protein, human; D003115:Colony-Stimulating Factors; D015850:Interleukin-6; D016209:Interleukin-8; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D003907:Dexamethasone