IL-1β and TNFα regulate sodium absorption in rat distal colon
IL-1β and TNFα regulate sodium absorption in rat distal colon
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DOI：
10.1016/j.bbrc.2004.03.072
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发表时间：
2004-04-30
影响因子：
3.1
通讯作者：
Schulzke, JD
中科院分区：
文献类型：
--
作者：
Barmeyer, C;Amasheh, S;Schulzke, JD
上皮Na+通道（ENaC）提供远端大肠的主要吸收途径。本研究旨在表征细胞因子对大鼠晚期远端结肠的调节影响。与 IL1beta、TNFα、IFNgamma 或 TNFα 和 IFNgamma 的组合孵育 6 小时后，在 Ussing 室中完全剥离的样本中用 3 nM 醛固酮 (J(Na)) 诱导 8 小时后，测量 ENaC 作为生电 Na+ 转运。随后，通过 Northern 印迹分析 α-、β- 和 γ-ENaC 亚基 mRNA。克隆 γ-ENaC 启动子并通过报告基因测定进行表征。 IL-1β 和 TNFα 会降低 J(Na)，但干扰素 γ 不会。同时，β-和γ-ENaC 转录受到抑制，而α-ENaC 不受影响。 γ-ENaC 启动子活性被 IL-1beta 和 TNFα 抑制，但不被 IFNgamma 抑制。我们得出的结论是，促炎细胞因子 IL-1β 和 TNFα 通过 β- 和 γ-ENaC 亚基的 mRNA 表达调节来抑制大鼠远端结肠的电化学钠吸收。 (C) 2004 Elsevier Inc. 保留所有权利。
The epithelial Na+ channel (ENaC) provides the main absorptive pathway of the distal large intestine. This study aimed to characterize regulatory influences of cytokines in rat late distal colon. After 6 h incubation with either IL1beta, TNFalpha, IFNgamma, or combinations of TNFalpha and IFNgamma, ENaC was measured as electrogenic Na+ transport after 8 h induction by 3 nM aldosterone (J(Na)) in totally stripped specimens in the Ussing chamber. Subsequently, alpha-, beta-, and gamma-ENaC subunit mRNAs were analyzed by Northern blotting. The gamma-ENaC promoter was cloned and characterized by reporter gene assays. IL-1beta and TNFalpha, but not interferon-gamma, decreased J(Na). In parallel, beta- and gamma-ENaC transcription was inhibited, whereas alpha-ENaC was unaffected. gamma-ENaC promoter activity was inhibited by IL-1beta and TNFalpha but not by IFNgamma. We conclude that the pro-inflammatory cytokines IL-1beta and TNFalpha inhibit electrogenic sodium absorption in rat distal colon by mRNA expression regulation of the beta- and gamma-ENaC subunits. (C) 2004 Elsevier Inc. All rights reserved.