title: Interleukin-6 stimulates epithelial sodium channels in mouse cortical collecting duct cells.
abstract: The aim of this study is to elucidate the effects of interleukin-6 (IL-6) on the expression and activity of the epithelial sodium channel (ENaC), which is one of the key mechanisms underlying tubular sodium reabsorption. M-1 cortical collecting duct cells were treated with IL-6 (100 ng/ml) for 12 h. Real-time polymerase chain reaction and immunoblotting were employed to examine the mRNA and protein abundance. Transepithelial voltage (V(te)) and resistance (R(te)) were measured with an ohm/voltmeter (EVOM, WPI). The equivalent current was calculated as the ratio of V(te) to R(te.) Treatment with IL-6 (n = 5) increased the mRNA abundance of alpha-ENaC by 11 +/- 7% (P = not significant), beta-ENaC by 78 +/- 14% (P = 0.01), gamma-ENaC by 185 +/- 38% (P = 0.02), and prostasin by 29 +/- 5% (P = 0.01), all normalized by beta-actin. Treatment with IL-6 increased the protein expression of alpha-ENaC by 19 +/- 3% (P = 0.001), beta-ENaC by 89 +/- 21% (P = 0.01), gamma-ENaC by 36 +/- 12% (P = 0.02), and prostasin by 33 +/- 6% (P = 0.02). The amiloride-sensitive sodium current increased by 37 +/- 5%, from 6.0 +/- 0.4 to 8.2 +/- 0.3 muA/cm(2) (P < 0.01), in the cells treated with IL-6 compared with controls (P = 0.01). Aprotinin (28 microg/ml), a prostasin inhibitor, reduced the amiloride-sensitive sodium current by 61 +/- 5%, from 6.1 +/- 0.3 to 3.7 +/- 0.2 muA/cm(2) (P = 0.01). The magnitude of the IL-6-induced amiloride-sensitive sodium current in the presence of aprotinin dropped by 57 +/- 2%, from 8.6 +/- 0.2 to 4.9 +/- 0.2 muA/cm(2) (P < 0.01). This study has identified a novel function of IL-6, namely, IL-6 may activate ENaC. Therefore, renal inflammation mediated by IL-6 likely contributes to impaired pressure natriuresis.
authors.affiliation: Georgia Prevention Institute, Dept. of Pediatrics, Medical College of Georgia, Augusta, GA 30912-3715, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.forename: Dehuang
authors.initials: D
authors.lastname: Guo
authors.forename: Haidong
authors.initials: H
authors.lastname: Zhu
authors.forename: Kathleen S
authors.initials: KS
authors.lastname: Hering-Smith
authors.forename: L Lee
authors.initials: LL
authors.lastname: Hamm
authors.forename: Jingping
authors.initials: J
authors.lastname: Ouyang
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Dong
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D017097:Electric Impedance; D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D015850:Interleukin-6 / Q000378:metabolism*; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D000099271:Prostasin
chemical_list: D000584:Amiloride; D007611:Aprotinin; D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels; D015850:Interleukin-6; D012333:RNA, Messenger; D012697:Serine Endopeptidases; D026941:Sodium Channel Blockers; D000099271:Prostasin; C507047:Scnn1a protein, mouse; C507049:Scnn1b protein, mouse; C507053:Scnn1g protein, mouse