Taurine chloramine inhibits the synthesis of nitric oxide and the release of tumor necrosis factor in activated RAW 264.7 cells

• Published in: Journal of leukocyte biology Vol. 54; no. 2; pp. 119 - 124
• Main Authors: Park, Eunkyue, Quinn, Michael R., Wright, Charles E., Schuller‐Levis, Georgia
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Society for Leukocyte Biology 01.08.1993; Federation of American Societies for Experimental Biology
• Subjects: Amino Acid Oxidoreductases - antagonists & inhibitors; Animals; Biological and medical sciences; Biological Transport; Cell Line; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Inflammation - metabolism; Interferon-gamma - pharmacology; interferon‐γ; lipopolysaccharide; Lipopolysaccharides - pharmacology; macrophage activation; Macrophage Activation - physiology; Mice; Monocytes, macrophages; Myeloid cells: ontogeny, maturation, markers, receptors; nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase; RAW 264.7; Recombinant Proteins; Taurine - analogs & derivatives; Taurine - metabolism; Taurine - physiology; taurine chloramine; tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; Cell culture; Vertebrata; Mammalia; Monocyte; Mouse; Tumor necrosis factor; Secretion; Rodentia; Cytokine; Nitrogen monoxide; Inhibition; Mechanism of action
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1002/jlb.54.2.119

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 amio‐ darone. Taurine is chlorinated to form taurine chloramine (Tau‐Cl) by the halide‐dependent myeloperoxidase system and, under physiological conditions, reduces HOC1 toxicity. Although NO and its metabolites, ΝO2− and NOs−, 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‐γ (rIFN‐γ; 50 U/ml) and lipopoly‐ saccharide (LPS; 10 μg/ml). NO was measured spec‐ trophotometrically as ΝO2− after reaction with Griess reagent and TNF was measured by FLISA. 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.