Affiliation:
1. Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Augusta, Georgia;
2. Medical College, Wuhan University, Wuhan, Hubei, People's Republic of China; and
3. Tulane University and Tulane Hypertension and Renal Center of Excellence New Orleans, Louisiana
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 Vteto Rte.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.
Publisher
American Physiological Society
Subject
Physiology (medical),Physiology
Cited by
63 articles.
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