Reduction of chemokine IL-8 and RANTES expression in human bronchial epithelial cells by a sea-water derived saline through inhibited nuclear factor-kappaB activation.
The NaCl content of airway surface fluid is believed to be of central importance in lung pathology. To test whether the Na+ concentration could influence the inflammatory response in human bronchial epithelial cells (BECs), we investigated the interleukin (IL)-8 and RANTES expression in BECs exposed to an isotonic sea-water derived low Na+ (ISW) saline compared to isotonic 0.9% NaCl saline. Exposure of BECs to ISW saline caused a significant decrease in IL-8 and RANTES gene expression and protein production as compared to that observed with 0.9% NaCl saline. Furthermore, we observed a concomitant reduction of phosphorylated IkappaBalpha associated with a marked inhibition of NF-kappaB-DNA binding activity in BECs exposed to ISW saline as compared to 0.9% NaCl saline. These findings support a new role for Na+ in the pathogenesis of airway inflammatory disorders. Therapies targeted at lowering Na+ level in airway epithelium may be beneficial in treating inflammatory lung diseases.
Tabary
Olivier
O
Inserm E213, Hôpital A.Trousseau, 75012 Paris, France.
Muselet
Céline
C
Miesch
Marie Claude
MC
Yvin
Jean Claude
JC
Clément
Annick
A
Jacquot
Jacky
J
D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis* / Q000235:genetics; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins / Q000187:drug effects / Q000378:metabolism*; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D007552:Isotonic Solutions / Q000494:pharmacology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism*; D012623:Seawater / Q000737:chemistry; D012964:Sodium / Q000737:chemistry; D012965:Sodium Chloride / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*
D018946:Chemokine CCL5; D018925:Chemokines; D020672:I-kappa B Proteins; D016209:Interleukin-8; D007552:Isotonic Solutions; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha; D012965:Sodium Chloride; D012964:Sodium