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

Abstract

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 IL1β, TNFα, IFNγ, or combinations of TNFα and IFNγ, 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, α-, β-, and γ-ENaC subunit mRNAs were analyzed by Northern blotting. The γ-ENaC promoter was cloned and characterized by reporter gene assays. IL-1β and TNFα, but not interferon-γ, decreased J Na. In parallel, β- and γ-ENaC transcription was inhibited, whereas α-ENaC was unaffected. γ-ENaC promoter activity was inhibited by IL-1β and TNFα but not by IFNγ. We conclude that the pro-inflammatory cytokines IL-1β and TNFα inhibit electrogenic sodium absorption in rat distal colon by mRNA expression regulation of the β- and γ-ENaC subunits.