Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 567, Issue 1-2, Pages 19-25Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2007.04.026
Keywords
epithelial sodium channel; interleukin-1 beta; middle ear
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Funding
- National Research Foundation of Korea [R01-2006-000-10100-0] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Recent reports have shown that cytokines inhibit fluid absorption by suppressing Na+ channel activity in various epithelia. In this study, we investigated the role of epithelial sodium channel (ENaC) in fluid absorption in normal human middle car epithelial (NHMEE) cells, as well as the effects of Interleukin (IL)-1 beta on ENaC expression and fluid absorption in NHMEE cells. We confirmed that ENaC alpha, beta and gamma were predominantly expressed on the apical surface of the NHMEE cells by immunocytochemistry. Addition of amiloride, a potent ENaC blocker, to apical membranes of NHMEE cells decreased the fluid absorption rate in a dose-dependent manner. Treatment with 10 ng/ml IL-1 beta for 24 h suppressed ENaC beta expression, the ENaC-dependent short-circuit current (Isc), and ENaC-dependent fluid absorption. When the NHMEE cells were pretreated with a phospholipase C (PLC)inhibitor (U73122, 10 mu M), a protein kinase C (PKC) inhibitor (Calphostin C, 0.1 mu M), or extracellular signal regulated kinase (ERK) 1/2 inhibitor (PD98059, 10 mu M), the amiloride-sensitive currents in IL-1 beta-treated cells were reversed to control levels; an effect not seen with SB202190 (an inhibitor of p38 mitogen-activated protein (MAP) kinase) or SP600125 (a reversible inhibitor of c-Jun N-terminal kinase). In this study we showed that ENaC is essential for fluid absorption in NHMEE cells and that IL-1 beta suppresses the ENaC- dependent current via the PLC-PKC-ERK1/2 pathway. These results suggest that IL-1 beta may contribute to fluid retention in otitis media with effusion by changing electrolyte transport and reducing middle ear epithelial fluid absorption. (c) 2007 Elsevier B.V. All rights reserved.
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