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Lipopolysaccharide increases Na+, K+ -pump, but not ENaC, expression in guinea-pig airway epithelium.

Authors
Dodrill-MW; Beezhold-DH; Meighan-T; Kashon-ML; Fedan-JS
Source
Eur J Pharm 2011 Jan; 651(1-3):176-186
NIOSHTIC No.
20038105
Abstract
Earlier, we found in functional experiments that lipopolysaccharide (LPS; 4 mg/kg; i.p.) hyperpolarized the epithelium by stimulating the transepithelial transport of Na+ in guinea-pig tracheal epithelium. Epithelial sodium channel (ENaC) activity and Na+,K+-pump activity were increased. In this study, we hypothesized that LPS increases the expression of ENaC and the Na+,K+-pump in the epithelium and investigated the levels of transcription and protein abundance. Using qPCR, the effects of LPS on the transcription of alphaENaC, alpha1 Na+,K+-pump, COX-2, eNOS, iNOS, IL-1, and TNF-alpha were measured at 3 and 18 h. In the epithelium, LPS increased the transcription of COX-2, IL-1, and, to a nonsignificant extent, TNF-alpha at 3 h, but not at 18 h. In alveolar macrophages, TNF-alpha, and, to a nonsignificant extent, COX-2 and IL-1 were up-regulated at 3 h, but not at 18 h. Even though LPS stimulated the transcription of some genes, alphaENaC and alpha1 Na+,K+-ATPase transcription were not affected. The expressions of alpha-, -, and gamma-ENaC and alpha1 Na+,K+-pump from the tracheal epithelium and kidney cortex/medulla were investigated by western blotting. All three ENaC subunits were detected as cleavage fragments, yet LPS had no effect on their expression. LPS increased the expression of the alpha1 subunit and the alpha1, alpha2, and alpha3 subunits, collectively, of the Na+,K+-pump. Taken together, these data indicate that LPS increases Na+ transport downstream of the genetic level, in part, by stimulating the expression of the Na+,K+-pump.
Keywords
Lung-cells; Lung-function; Animal-studies; Laboratory-animals Endotoxins; Pharmacodynamics; Alveolar-cells; Pulmonary-function; Mucous-membranes; Transport-mechanisms; Genes; Polysaccharides; Cellular-transport-mechanism; Author Keywords: Endotoxin; Lung; Airway epithelium; Epithelial sodium channel (ENaC); Sodium; Potassium ATPase (Na+,K+-ATPase)
Contact
Jeffrey S. Fedan, National Institute for Occupational Safety and Health, Health Effects Laboratory Division,1095 Willowdale Road, Morgantown, WV 26505, USA
CODEN
EJPHAZ
Publication Date
20110125
Document Type
Journal Article
Email Address
jsf2@cdc.gov
Fiscal Year
2011
NTIS Accession No.
NTIS Price
Issue of Publication
1-3
ISSN
0014-2999
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
European Journal of Pharmacology
State
WV
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