Chemokine expression in CF epithelia: implications for the role of CFTR in RANTES expression

To delineate themechanisms that facilitate leukocyte migration into the cystic fibrosis(CF) lung, expression of chemokines, including interleukin-8 (IL-8),monocyte chemoattractant protein-1 (MCP-1), andRANTES, was compared between CF and non-CF airway epithelia. Thefindings presented herein demonstrate that, under either basalconditions or tumor necrosis factor- (TNF-)- and/or interferon- (IFN-)-stimulated conditions, a consistent pattern ofdifferences in the secretion of IL-8 and MCP-1 between CF and non-CFepithelial cells was not observed. In contrast, CF epithelial cellsexpressed no detectable RANTES protein or mRNA under basal conditionsor when stimulated with TNF- and/or IFN-(P  0.05), unlike their non-CFcounterparts. Correction of the CF transmembrane conductance regulator(CFTR) defect in CF airway epithelial cells restored the induction ofRANTES protein and mRNA by TNF- in combination with IFN-(P  0.05) but had little effect onIL-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 that1) RANTES expression is altered inCF epithelia and 2) epithelialexpression of RANTES, but not IL-8 or MCP-1, is dependent on CFTR.