Interleukin-6 stimulates epithelial sodium channels in mouse cortical collecting duct cells

Ke Li, Dehuang Guo, Haidong Zhu, Kathleen S. Hering-Smith, L. Lee Hamm, Jingping Ouyang, Yanbin Dong

Research output: Contribution to journalArticle

37 Scopus citations

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 (Vte) and resistance (Rte) were measured with an ohm/ voltmeter (EVOM, WPI). The equivalent current was calculated as the ratio of Vte to R te. Treatment with IL-6 (n = 5) increased the mRNA abundance of α-ENaC by 11 ± 7% (P = not significant), β-ENaC by 78 ± 14% (P = 0.01), γ-ENaC by 185 ± 38% (P = 0.02), and prostasin by 29 ± 5% (P = 0.01), all normalized by β-actin. Treatment with IL-6 increased the protein expression of α-ENaC by 19 ± 3% (P = 0.001), β-ENaC by 89 ± 21% (P = 0.01), γ-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 μA/cm2 (P < 0.01), in the cells treated with IL-6 compared with controls (P = 0.01). Aprotinin (28 μg/ml), a prostasin inhibitor, reduced the amiloride-sensitive sodium current by 61 ± 5%, from 6.1 ± 0.3 to 3.7 ± 0.2 μA/cm2 (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 μA/cm2 (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.

Original languageEnglish (US)
Pages (from-to)R590-R595
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume299
Issue number2
DOIs
StatePublished - Aug 1 2010

Keywords

  • Distal tubule
  • Pressure natriuresis
  • Prostasin

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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