The regulation of amiloride-sensitive epithelial sodium channels by tumor necrosis factor-alpha in injured lungs and alveolar type II cells

Toshiyuki Yamagata, Yuko Yamagata, Takeshi Nishimoto, Tsunahiko Hirano, Masanori Nakanishi, Yoshiaki Minakata, Masakazu Ichinose, André Dagenais, Yves Berthiaume

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Alveolar liquid clearance, which mainly depends on sodium transport in alveolar epithelial cells, is an important mechanism by which excess water in the alveoli is reabsorbed during the resolution of pulmonary edema. In this study, we examined the regulation of epithelial sodium channel (ENaC), the main contributor to sodium transport, during acute lung injury and the direct impact of tumor necrosis factor-alpha (TNF-α), one of the important cytokines in acute lung injury, on the ENaC regulation. During the development of pulmonary edema, the increases in the number of neutrophils and the levels of TNF-α in blood and bronchoalveolar lavage were seen. In parallel, the mRNA expression of the α-, β- and γ-ENaC subunits in the whole lung tissue was inhibited to 72.0, 47.8 and 53.9%, respectively. The direct exposure of rat alveolar type II cells to TNF-α inhibited the mRNA expression of α- and γ-ENaC to 64.0 and 78.0%, but not that of the β-ENaC. TNF-α also inhibited the ENaC function as indicated by the reduction of amiloride-sensitive current (control 4.4, TNF-α 1.9 μA/cm2). These data suggest that TNF-α may affect the pathophysiology of acute lung injury and pulmonary edema through the inhibition of alveolar liquid clearance and sodium transport.

Original languageEnglish
Pages (from-to)16-23
Number of pages8
JournalRespiratory Physiology and Neurobiology
Volume166
Issue number1
DOIs
Publication statusPublished - 2009 Mar 31
Externally publishedYes

Keywords

  • Alveolar liquid clearance
  • Epithelial sodium channel
  • Phorbol ester
  • Sodium transport
  • Tumor necrosis factor-alpha

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pulmonary and Respiratory Medicine

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