Taurine blunts LPS‐induced increases in intracellular calcium and TNF‐α production by Kupffer cells

Activation of Kupffer cells by lipopolysaccharide (LPS) plays a pivotal role in the onset of pathophysiological events that occur during endotoxemia and intracellular calcium ([Ca 2+ ] i ) is involved in LPS‐stimulated cytokine production. Recently, it was shown that Kupffer cells contain a glycine‐gated chloride channel. Because taurine, a ubiquitous sulfur‐containing β‐amino acid, acts similarly to glycine in neurons by causing hyperpolarization, it was hypothesized that taurine would act via a similar mechanism, blunting the LPS‐induced increase in [Ca 2+ ] i in Kupffer cells. To test this hypothesis, Kupffer cells were isolated from female Sprague‐Dawley rats and cultured for 24 h. LPS‐induced changes in [Ca 2+ ] i were monitored fluorometrically in single cells, whereas levels of tumor necrosis factor α (TNF‐α) released by Kupffer cells after exposure to LPS were measured by enzyme‐linked immunosorbent assay. Taurine significantly blunted the LPS‐induced increase in [Ca 2+ ] i in a dose‐dependent manner (IC 50 , 0.1 mM). This effect was reversed by strychnine (1 μM) and was prevented when chloride was removed from the extracellular media. Moreover, taurine increased 36 Cl – uptake by Kupffer cells in a dose‐dependent manner (EC 50 , 0.2 mM). Furthermore, strychnine (1 μM) reversed the effect of taurine on 36 Cl – uptake. These results indicate that taurine activates a glycine‐gated chloride channel in Kupffer cells causing chloride influx. In addition, LPS‐induced TNF‐α production was reduced by more than 40% by taurine, an effect that was also reversed by strychnine. In conclusion, taurine blocks the increase in [Ca 2+ ] i due to LPS and significantly reduces TNF‐α production by mechanisms involving chloride influx into the Kupffer cell. J. Leukoc. Biol. 64: 615–621; 1998.