Polymorphonuclear leukocytes (PMN, neutrophils) are inflammatory cells that possess halide-dependent myeloperoxidase (MPO). Activated PMN secrete MPO and release it upon death. MPO produces HOCl/OCl-, which reacts with taurine to form taurine monochloramine (Tau-Cl), a more stable and selective oxidant than HOCl/OCl. Elevated levels of extracellular taurine increase Tau-Cl concentrations at the site of inflammation via PMN associated MPO activity. It is our hypothesis that prophylactic administration of taurine may attenuate tissue damage resulting from aberrant inflammatory responses through formation of Tau-Cl and subsequent inhibition of the production of proinflammatory mediators. Astrocytes and microglia are a major source of tissue damaging proinflammatory mediators in the CNS and contribute to the neural damage that occurs during ischemic stroke. The primary goals of this proposal are to establish the inhibitory effects of Tau-Cl on the production of inflammatory mediators by activated glial cells and to determine the molecular mechanisms(s) through which Tau-Cl exerts this effect. This will be accomplished using primary cultures of rat astrocytes and microglia, and clonal cell lines derived from glial cells. The ability of Tau-Cl to inhibit production of proinflammatory mediators will be evaluated in a model of CNS hypoxic ischemia using culture systems of rat glial cells for in vitro studies. In addition, a rat model of transient middle cerebral artery occlusion will be used for in vivo studies of the efficacy of taurine to protect against the CNS damage that results from transient focal cerebral ischemia. Completion of these studies is not only important to determining the mechanism of Tau-Cl action in cells of neural origin, as occurs in ischemic and traumatic brain injury, but may also be relevant to modulating inflammatory responses in general.
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| Quinn, Michael R; Barua, Madhabi; Liu, Yong et al. (2003) Taurine chloramine inhibits production of inflammatory mediators and iNOS gene expression in alveolar macrophages; a tale of two pathways: part I, NF-kappaB signaling. Adv Exp Med Biol 526:341-8 |
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| Liu, Yong; Barua, Madhabi; Serban, Valeria et al. (2003) Production of inflammatory mediators by activated C6 cells is attenuated by taurine chloramine inhibition of NF-kappaB activation. Adv Exp Med Biol 526:365-72 |
