Taurine chloramine inhibits the synthesis of nitric oxide and the release of tumor necrosis factor in activated RAW 264.7 cells.
Taurine is present in high concentrations in most mammalian tissues, including those that prodigiously produce oxidants. Taurine protects against bronchiolar damage induced by NO2, ozone, bleomycin, and amiodarone. Taurine is chlorinated to form taurine chloramine (Tau-Cl) by the halide-dependent myeloperoxidase system and, under physiological conditions, reduces HOCl toxicity. Although NO and its metabolites, NO2- and NO3-, are thought to be major mediators of tissue damage resulting from oxidant exposure, cytokines, including tumor necrosis factor (TNF), are also involved. We examined the effects of Tau-Cl on NO production and TNF release by using RAW 264.7 cells activated with recombinant interferon-gamma (rIFN-gamma; 50 U/ml) and lipopolysaccharide (LPS; 10 micrograms/ml). NO was measured spectrophotometrically as NO2- after reaction with Griess reagent and TNF was measured by ELISA. Tau-Cl (0.5 mM) inhibits NO and TNF released into the medium by 47% and 43%, respectively. Tau-Cl is actively transported into RAW 264.7 cells by an uptake system that is energy, temperature, and Na+ dependent. Competition experiments demonstrate that the uptake system for Tau-Cl is distinct from that for taurine. In addition, the NO synthase activity of cytosolic preparations from activated RAW 264.7 cells is irreversibly inhibited by pretreatment with Tau-Cl. We demonstrate that Tau-Cl inhibits production of NO and TNF by activated macrophages and suggest a mechanism through which taurine supplementation may protect against oxidant-induced tissue damage.
Park
E
E
Department of Immunology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
Quinn
M R
MR
Wright
C E
CE
Schuller-Levis
G
G
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D007249:Inflammation / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000502:physiology*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D011994:Recombinant Proteins; D013654:Taurine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D013654:Taurine; D009569:Nitric Oxide; C043410:N-chlorotaurine; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases