ABCMdb

PMID: 16647268

Chan MM, Chmura K, Chan ED
Increased NaCl-induced interleukin-8 production by human bronchial epithelial cells is enhanced by the DeltaF508/W1282X mutation of the cystic fibrosis transmembrane conductance regulator gene.
Cytokine. 2006 Mar 21;33(6):309-16. Epub 2006 Apr 27., [PubMed]

Sentences

No. Mutations Sentence Comment

2 ABCC7 p.Trp1282* The objectives of this study were: (i) to determine the relative contribution of three potential cis-regulatory elements in the regulation of NaCl-induced IL-8 production in BEAS-2B human bronchial epithelial cells, (ii) to compare NaCl-induced IL-8 expression in IB3-1 bronchial epithelial cells, which have the DF508/W1282X mutation of the CF transmembrane conductance regulator (CFTR) gene, with that in C38 cells, which are IB3-1 cells stably transfected with a truncated but functional CFTR gene, and (iii) to compare equal osmolar concentrations of NaCl and D-sorbitol in the induction of IL-8 in all three cell types. Login to comment 4 ABCC7 p.Trp1282* Human bronchial epithelial cells with the DF508/W1282X CFTR mutation produce an exaggerated amount of basal and NaCl-induced IL-8. Login to comment 49 ABCC7 p.Trp1282* IB3-1 epithelial cells were derived from a CF patient with a compound heterozygous mutation of CFTR (DF508/W1282X) [30]. Login to comment 125 ABCC7 p.Trp1282* IB3-1 epithelial cells with the DF508/W1282X CFTR mutation produces more IL-8 basally and with osmotic stimulation than cells rescued with a functioning CFTR Since epithelial cells in CF individuals have a defect in the CFTR membrane protein, we investigated whether a Clÿ channel defect affects IL-8 production in response to NaCl or D-sorbitol. Login to comment 127 ABCC7 p.Trp1282* The IB3-1 cells exhibit the DF508/W1282X CFTR mutation. Login to comment 134 ABCC7 p.Trp1282* Discussion In this study, we showed that: (i) NaCl increased IL-8 protein expression in human bronchial epithelial cells, (ii) BEAS-2B cells were more sensitive to NaCl stimulation in that IL-8 expression was increased and toxicity occurred at lower concentrations compared to equivalent osmolarity of D-sorbitol, (iii) the binding sites for NFkB, AP-1, and NF-IL-6 play important regulatory roles in the induction of IL-8 by NaCl, (iv) bronchial epithelial cells with defective CFTR (DF508/ W1282X) produced significantly more IL-8 constitutively and in response to NaCl stimulation than cells with functioning CFTR, and (v) in contrast to BEAS-2B cells, IB3-1 and C38 human bronchial epithelial cells were more sensitive to D-sorbitol than to equiosmolar concentrations of NaCl. Login to comment 179 ABCC7 p.Trp1282* (A) IB3-1 cells with defective CFTR due to a DF508/W1282X mutation and C38 cells in which wild-type CFTR has been stably transfected were stimulated with NaCl at the indicated concentrations for 48 h and the cell supernatants assayed for IL-8. Login to comment 192 ABCC7 p.Trp1282* Indeed, airway epithelial cells with either the DF508/DF508 or the DF508/W1282X CFTR mutation produce more IL-8 in response to TNFa [46] or to infection with Pseudomonas aeruginosa [47,48]. Login to comment