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Baines, D. L., Albert, A. P. 
ORCID: https://orcid.org/0000-0002-3596-9634, Házeli, M. J., Gambling, L., Woollhead, A. M. and Dockrell, M. E. C.
(2010)
Lipopolysaccharide modifies amiloride-sensitive Na+ transport processes across human airway cells: Role of mitogen-activated protein kinases ERK 1/2 and 5.
Pflugers Archiv European Journal of Physiology, 459 (3).
pp. 451-463.
ISSN 0031-6768
Abstract
Bacterial lipopolysaccharides (LPS) are potent inducers of proinflammatory signaling pathways via the activation of nuclear factor-kappa B (NF-KB) and mitogenactivated protein kinase (MAPK), causing changes in the processes that control lung fluid homeostasis and contributing to the pathogenesis of lung disease. In human H441 airway epithelial cells, incubation of cells with 15 ng ml-1 LPS caused a significant reduction in amiloride-sensitive / sc from 15±2 to 8±2 uA cm-2 (p=0.01, n=13) and a shift in IC50 amiloride of currents from 6.8 × 10 -7 to 6.4×10-6 M. This effect was associated with a decrease in the activity of 5 pS, highly Na+ selective, amiloride-sensitive <1 u.M. channels (HSC) and an increase in the activity of ∼18 pS, nonselective, amiloride-sensitive >10 uM cation channels (NSC) in the apical membrane. LPS decreased aENaC mRNA and protein abundance, inferring that LPS inhibited aENaC gene expression. This correlated with the decrease in HSC activity, indicating that these channels, but not NSCs, were comprised of at least aENaC protein. LPS increased NF- KB DNA binding activity and phosphorylation of extracellular signal-related kinase (ERK) 1/2, but decreased phosphorylation of ERKS in H.441 cells. Pretreatment of monolayers with PD98059 (20 uM) inhibited ERK1/2 phosphorylation, promoted phosphorylation of ERK5, increased aENaC protein abundance, and reversed the effect of LPS on I80 and the shift in amiloride sensitivity. Inhibitors of NF-KB activation were without effect. Taken together, our data indicate that LPS acts via ERK signaling pathways to decrease ccENaC transcription, reducing HSC/ ENaC channel abundance, activity, and transepithelial Na+ transport in H441 airway epithelial cells.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding information: Wellcome Trust (068674/Z/02) and BBSRC (BB/E013597/1) |
| Uncontrolled Keywords: | airway,amiloride,erk,lps,lung,na channel,physiology,clinical biochemistry,physiology (medical),sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1300/1314 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 29 Oct 2024 09:30 |
| Last Modified: | 05 Nov 2024 16:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/97263 |
| DOI: | 10.1007/s00424-009-0717-4 |
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