title: The regulation of amiloride-sensitive epithelial sodium channels by tumor necrosis factor-alpha in injured lungs and alveolar type II cells.
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-alpha), 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-alpha in blood and bronchoalveolar lavage were seen. In parallel, the mRNA expression of the alpha-, beta- and gamma-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-alpha inhibited the mRNA expression of alpha- and gamma-ENaC to 64.0 and 78.0%, but not that of the beta-ENaC. TNF-alpha also inhibited the ENaC function as indicated by the reduction of amiloride-sensitive current (control 4.4, TNF-alpha 1.9 microA/cm(2)). These data suggest that TNF-alpha may affect the pathophysiology of acute lung injury and pulmonary edema through the inhibition of alveolar liquid clearance and sodium transport.
authors.affiliation: Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, 811-1, Kimiidera, Wakayama 641-8509, Japan. yamagata@jtw.zaq.ne.jp
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamagata
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yamagata
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishimoto
authors.forename: Tsunahiko
authors.initials: T
authors.lastname: Hirano
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakanishi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Minakata
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ichinose
authors.forename: André
authors.initials: A
authors.lastname: Dagenais
authors.forename: Yves
authors.initials: Y
authors.lastname: Berthiaume
mesh_terms: D055371:Acute Lung Injury / Q000473:pathology*; D000584:Amiloride / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology; D014867:Water / Q000378:metabolism
chemical_list: D053503:Epithelial Sodium Channels; D012333:RNA, Messenger; D026941:Sodium Channel Blockers; D014409:Tumor Necrosis Factor-alpha; D014867:Water; D000584:Amiloride