Background/aims: The availability of betaine as an osmolyte was recently shown to interfere strongly with important cell functions of liver macrophages (Kupffer cells), such as eicosanoid and tumor necrosis factor-alpha production or phagocytosis. We therefore investigated whether taurine is also used as an osmolyte by Kupffer cells and whether it is involved in the control of Kupffer cell functions.
Methods/results: Hyperosmotic (hypoosmotic) exposure of cultured rat liver macrophages (Kupffer cells) for 6-12 h led to an increase (decrease) in the mRNA levels of the taurine transporter (TAUT) and an increase (decrease) in taurine transport into the cells. The hyperosmolarity-induced increase in TAUT-mRNA levels was diminished by 37+/-10% upon addition of taurine, but not upon addition of betaine. When Kupffer cells were preloaded with taurine, hypoosmotic exposure led to a rapid efflux of taurine from the cells, which was significantly delayed in the presence of the anion exchanger inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). Taurine efflux was also stimulated during phagocytosis of Latex particles; however, Latex was without effect on the hyperosmolarity-induced increase of TAUT mRNA levels. Lipopolysaccharide (LPS) led to an induction of cyclooxygenase-2, which was markedly enhanced during hyperosmotic conditions. Taurine diminished the induction of cyclooxygenase-2 and inhibited the LPS/hyperosmolarity-induced stimulation of prostaglandin E2 formation.
Conclusions: The data suggest that, in addition to betaine, taurine also acts as an osmolyte in Kupffer cells, and that taurine availability may be an important modulater of Kupffer cell functions such as eicosanoid synthesis.