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Chemokine expression in CF epithelia: implications for the role of CFTR in RANTES expression
1 Department of Physiology and Biophysics and 2 Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama, Birmingham, Alabama 35294 To delineate the mechanisms that facilitate leukocyte migration into the cystic fibrosis (CF) lung, expression of chemokines, including interleuki...
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Published in: | American Journal of Physiology: Cell Physiology 1999-03, Vol.276 (3), p.C700-C710 |
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Main Authors: | , , |
Format: | Article |
Language: | English |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 1 Department of Physiology and
Biophysics and 2 Gregory Fleming
James Cystic Fibrosis Research Center, University of Alabama,
Birmingham, Alabama 35294
To delineate the
mechanisms that facilitate leukocyte migration into the cystic fibrosis
(CF) lung, expression of chemokines, including interleukin-8 (IL-8),
monocyte chemoattractant protein-1 (MCP-1), and
RANTES, was compared between CF and non-CF airway epithelia. The
findings presented herein demonstrate that, under either basal
conditions or tumor necrosis factor- (TNF- )- and/or interferon- (IFN- )-stimulated conditions, a consistent pattern of
differences in the secretion of IL-8 and MCP-1 between CF and non-CF
epithelial cells was not observed. In contrast, CF epithelial cells
expressed no detectable RANTES protein or mRNA under basal conditions
or when stimulated with TNF- and/or IFN-
( P 0.05), unlike their non-CF
counterparts. Correction of the CF transmembrane conductance regulator
(CFTR) defect in CF airway epithelial cells restored the induction of
RANTES protein and mRNA by TNF- in combination with IFN-
( P 0.05) but had little effect on
IL-8 or MCP-1 production compared with mock controls. Transfection studies utilizing RANTES promoter constructs suggested that CFTR activates the RANTES promoter via a nuclear factor- B-mediated pathway. Together, these results suggest that
1 ) RANTES expression is altered in
CF epithelia and 2 ) epithelial
expression of RANTES, but not IL-8 or MCP-1, is dependent on CFTR.
epithelial cells; cystic fibrosis; cystic fibrosis transmembrane
conductance regulator; inflammation |
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ISSN: | 0363-6143 1522-1563 |
DOI: | 10.1152/ajpcell.1999.276.3.c700 |