IL-1β and TNFα regulate sodium absorption in rat distal colon

被引:46
作者
Barmeyer, C
Amasheh, S
Tavalali, S
Mankertz, J
Zeitz, M
Fromm, M
Schulzke, JD
机构
[1] Charite Univ Med Berlin, Dept Gastroenterol Infect Dis & Rheumatol, D-12200 Berlin, Germany
[2] Charite Univ Med Berlin, Dept Clin Physiol, D-12200 Berlin, Germany
关键词
colon; electrogenic Na+ absorption; epithelial sodium channel; interferon-gamma; interleukin-1; beta; pro-inflammatory cytokines; TNF alpha;
D O I
10.1016/j.bbrc.2004.03.072
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:500 / 507
页数:8
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