IL-1beta and TNFalpha regulate sodium absorption in rat distal colon.
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.
Barmeyer
Christian
C
Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité University Medicine Berlin, 12200 Berlin, Germany.
Amasheh
Salah
S
Tavalali
Shida
S
Mankertz
Joachim
J
Zeitz
Martin
M
Fromm
Michael
M
Schulzke
Jörg-Dieter
JD
D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D053503:Epithelial Sodium Channels; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D008297:Male; D051381:Rats; D012964:Sodium / Q000493:pharmacokinetics*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D053503:Epithelial Sodium Channels; D007375:Interleukin-1; D015222:Sodium Channels; D014409:Tumor Necrosis Factor-alpha; D000450:Aldosterone; D007371:Interferon-gamma; D012964:Sodium