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

Seabra, Vítor; Stachlewitz, Robert F.; Thurman, Ronald G.

doi:10.1002/jlb.64.5.615

Cited by 60 publications

(48 citation statements)

References 47 publications

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“…Moreover, the macrophages of taut Ϫ/Ϫ mice appear to change their stability in response to malaria, as circumstantially indicated by the increased systemic levels of TNF-␣ and IL-1␤, which are produced primarily by macrophages. This accords with other data showing, conversely, that taurine is able to dampen the effect of proinflammatory cytokines, including IL-1␤ (12) and TNF-␣ (10,24,33,34,44,47,60).…”

Section: Discussionsupporting

confidence: 92%

Loss of Ability To Self-Heal Malaria upon Taurine Transporter Deletion

et al. 2010

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Deletion of the taurine transporter gene (taut) results in lowered levels of taurine, the most abundant amino acid in mammals. Here, we show that taut ؊/؊ mice have lost their ability to self-heal blood-stage infections with Plasmodium chabaudi malaria. All taut ؊/؊ mice succumb to infections during crisis, while about 90% of the control taut ؉/؉ mice survive. The latter retain unchanged taurine levels even at peak parasitemia. Deletion of taut, however, results in the lowering of circulating taurine levels from 540 to 264 mol/liter, and infections cause additional lowering to 192 mol/liter. Peak parasitemia levels in taut ؊/؊ mice are approximately 60% higher than those in taut ؉/؉ mice, an elevation that is associated with increased systemic tumor necrosis factor alpha (TNF-␣) and interleukin-1␤ (IL-1␤) levels, as well as with liver injuries. The latter manifest as increased systemic ammonia levels, a perturbed capacity to entrap injected particles, and increased expression of genes encoding TNF-␣, IL-1␤, IL-6, inducible nitric oxide synthase (iNOS), NF-B, and vitamin D receptor (VDR). Autopsy reveals multiorgan failure as the cause of death for malaria-infected taut ؊/؊ mice. Our data indicate that taut-controlled taurine homeostasis is essential for resistance to P. chabaudi malaria. Taurine deficiency due to taut deletion, however, impairs the eryptosis of P. chabaudi-parasitized erythrocytes and expedites increases in systemic TNF-␣, IL-1␤, and ammonia levels, presumably contributing to multiorgan failure in P. chabaudi-infected taut ؊/؊ mice.

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Section: Discussionsupporting

confidence: 92%

Loss of Ability To Self-Heal Malaria upon Taurine Transporter Deletion

et al. 2010

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“…17 It has been shown that other amino acids such as glycine, ␤-alanine, and taurine also blunt the increase in intracellular calcium by LPS via a similar mechanism. 17,36 In support of this hypothesis, these phenomena were antagonized by strychnine, dependent on extracellular chloride, and associated with a large influx of radiolabeled chloride. 30 Because GSH and cysteinyl-glycine also blunted the increase in Ca 2ϩ due to LPS, it is proposed here that a part of the protective action of OTC is via actions of circulating GSH and GSH derivatives on Kupffer cells (Fig.…”

Section: Discussionmentioning

confidence: 81%

The glutathione precursor l-2-oxothiazolidine-4-carboxylic acid protects against liver injury due to chronic enteral ethanol exposure in the rat

et al. 2000

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L-2-oxothiazolidine-4-carboxylic acid (OTC) is a cysteine prodrug that maintains glutathione in tissues. Here, its effect on alcohol-induced liver injury in an enteral alcohol feeding model was investigated. Male Wistar rats were given control high-fat or ethanol containing diets enterally for 4 weeks. Treated rats received 500 mg/kg/d of dietary OTC. Ethanol delivery, weight gain, and the cyclic pattern of ethanol in the urine were not different between the OTC-ethanol and ethanol groups. After 4 weeks, serum aspartate transaminase (AST), necrosis and inflammation were elevated significantly by ethanol compared with appropriate high-fat controls, effects blocked by OTC. Moreover, ethanol elevated hepatic tumor necrosis factor ␣ (TNF-␣) messenger RNA (mRNA) and the nuclear transcription factor nuclear factor B (NFB) 2-3 fold. NFB in isolated Kupffer cells was also increased by ethanol. These effects were all blocked by OTC treatment. Additionally, superoxide production was higher in Kupffer cells isolated from ethanol-treated rats, an effect blunted by OTC. OTC also increased circulating glutathione (GSH) levels about 2-fold; however, GSH levels were not affected by ethanol or OTC in livers from the groups studied. Surprisingly, GSH was elevated by ethanol and OTC treatment in isolated Kupffer cells about 2-fold. Moreover, GSH (Ki-10 mol/L) and cysteinylglycine, but not oxidized glutathione (GSSG) or OTC, blunted the LPS-induced increase in calcium in isolated Kupffer cells, possibly by activating a glycine-gated chloride channel due to their structural similarity with glycine. Collectively, it is concluded that GSH is protective, in part, by increasing circulating GSH, which blunts activation of Kupffer cells via the glycine-gated chloride channel. (HEPATOLOGY 2000;31:391-398.)Kupffer cells release numerous mediators that participate in metabolic regulation, inflammation, and immune function. 1,2 Recent work from this laboratory has shown a central role for Kupffer cells in mechanisms of alcohol-induced liver injury. For example, when Kupffer cells were destroyed using gadolinium chloride (GdCl 3 ), injury caused by chronic alcohol administration in the Tsukamoto-French enteral alcohol feeding model was blocked. 3 Moreover, Kupffer cells are activated by bacterial endotoxin, and elimination of endotoxin with antibiotics 4 or Lactobacillus feeding 5 also diminished injury to the liver caused by alcohol. This concept was further strengthened by the observation that an antibody to tumor necrosis factor ␣ (TNF-␣) and a mouse lacking the TNF-receptor 1 6 exhibited diminished injury due to chronic ethanol 7 (for review see Thurman 8 ).Using the same enteral feeding model, Hirano et al. 9 showed that ethanol decreased hepatic glutathione (GSH) levels. Decreased glutathione occurs in many disease states including ischemia-reperfusion associated with heart disease. 10 Interestingly, they also showed that ethanol had a more pronounced effect on mitochondrial GSH content, and suggested that it could play an important role...

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“…As Ca 2ϩ -dependent mechanisms are involved in cytokine production and release by macrophages and neutrophils (17,18), it was tempting to speculate that nLDL are also able to potentiate synthesis of proinflammatory cytokines through Ca 2ϩ -dependent mechanisms. As previously shown in vascular endothelial cells (16), we were able to document an oscillatory pattern of Ca 2ϩ mobilization by nLDL in human PBMC.…”

Section: Discussionmentioning

confidence: 99%

“…Allen and colleagues have shown that nLDL induces expression of VCAM-1 and E-selectin in human vascular endothelial cells, and this is mediated through induction of Ca 2 ϩ mobilization (16). Interestingly, it has been demonstrated that Ca 2 ϩ -dependent mechanisms are directly involved in cytokine production and release by macrophages and neutrophils (17,18), and induction of TNF by acetylated LDL is also a Ca 2 ϩ -dependent phenomenon (8). It is therefore tempting to speculate that nLDLs are also able to potentiate spontaneous and/or stimulated production of proinflammatory cytokines by bloodstream human monocytes through Ca 2 ϩ -dependent mechanisms, contributing in this way to the development of atherosclerosis.…”

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confidence: 99%