Barmeyer Christian, Amasheh Salah, Tavalali Shida, Mankertz Joachim, Zeitz Martin, Fromm Michael, Schulzke Jörg-Dieter
Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité University Medicine Berlin, 12200 Berlin, Germany.
Biochem Biophys Res Commun. 2004 Apr 30;317(2):500-7. doi: 10.1016/j.bbrc.2004.03.072.
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 (JNa) 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 JNa. 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.
上皮钠通道（ENaC）是远端大肠主要的吸收途径。本研究旨在阐明细胞因子对大鼠远端结肠晚期的调节作用。将标本与白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、γ-干扰素（IFN-γ）或TNF-α与IFN-γ的组合一起孵育6小时后，在Ussing chamber中用3 nM醛固酮诱导8小时后，将ENaC测定为电致钠转运（JNa）。随后，通过Northern印迹分析α-、β-和γ-ENaC亚基的mRNA。通过报告基因分析克隆并鉴定γ-ENaC启动子。IL-1β和TNF-α可降低JNa，但干扰素-γ无此作用。同时，β-和γ-ENaC的转录受到抑制，而α-ENaC不受影响。IL-1β和TNF-α可抑制γ-ENaC启动子活性，但IFN-γ无此作用。我们得出结论，促炎细胞因子IL-1β和TNF-α通过调节β-和γ-ENaC亚基的mRNA表达来抑制大鼠远端结肠的电致钠吸收。
