Taurine chloramine inhibits inducible nitric oxide synthase and TNF-α gene expression in activated alveolar macrophages:: Decreased NF-κB activation and IκB kinase activity
Taurine chloramine inhibits inducible nitric oxide synthase and TNF-α gene expression in activated alveolar macrophages:: Decreased NF-κB activation and IκB kinase activity
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DOI：
10.4049/jimmunol.167.4.2275
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发表时间：
2001-08-15
影响因子：
4.4
通讯作者：
Quinn, MR
中科院分区：
文献类型：
--
作者：
Barua, M;Liu, Y;Quinn, MR
牛磺酸可预防多种炎症模型中的组织损伤，包括氧化剂诱导的肺损伤。保护机制尚不确定，但推测涉及通过与中性粒细胞相关的卤化物依赖性髓过氧化物酶衍生的牛磺酸氯胺（Tau-Cl）的作用。了解Tau-Cl对肺泡巨噬细胞产生炎症介质的影响，为确定Tau-Cl作用机制提供了机会。评价了Tau-Cl对NR 8383（一种源自大鼠肺泡巨噬细胞（RAM）的克隆细胞系）和RAM原代培养物中NO和TNF-α产生的影响。在激活的NR 8383细胞和RAM中，Tau-Cl抑制NO和TNF-α的产生以及诱导型NO合酶的表达。在NR 8383细胞中，Tau-Cl降低诱导型NO合酶和TNF-α mRNA的时间（2、4、8、24 h）表达。Tau-Cl抑制NF-κ B迁移到活化的NR 8383细胞的细胞核中，并导致I κ B在细胞质中更持续的存在。Tau-Cl处理的细胞中细胞质I kappaB-α的稳定化是由于I kappaB-α丝氨酸-32的磷酸化降低和I kappaB激酶（IKK）的活性降低。另外的实验证明Tau-Cl不直接抑制IKK活性。这些结果表明，Tau-Cl在信号通路中IKK上游的一定水平发挥其作用，并通过至少部分涉及抑制NF-κ B活化的机制抑制炎症介质的产生。
Taurine prevents tissue damage in a variety of models that involve inflammation, including oxidant-induced lung damage. The mechanism of protection is uncertain, but is postulated to involve the actions of taurine chloramine (Tau-Cl) derived via halide-dependent myeloperoxidase associated with neutrophils. Understanding the influence of Tau-Cl on the production of inflammatory mediators by alveolar macrophages provides an opportunity for determining the mechanism of Tau-CI action. The effects of Tau-Cl were evaluated on the production of NO and TNF-alpha in NR8383, a cloned cell line derived from rat alveolar macrophages (RAM), and in primary cultures of RAM. Production of NO and TNF-alpha, and expression of inducible NO synthase was inhibited by Tau-Cl in activated NR8383 cells as well as in RAM. Temporal (2, 4, 8, 24 h) expression of inducible NO synthase and TNF-a mRNAs was reduced by Tau-Cl in NR8383 cells. Tau-Cl depressed NF-kappaB migration into the nucleus of activated NR8383 cells and caused a more sustained presence of I kappaB in the cytoplasm. Stabilization of cytoplasmic I kappaB-alpha in Tau-Cl-treated cells resulted from decreased phosphorylation of I kappaB-alpha serine-32 and a lower activity of I kappaB kinase (IKK). Additional experiments demonstrated that Tau-Cl does not directly inhibit IKK activity. These results suggest that Tau-Cl exerts its effects at some level upstream of IKK in the signaling pathway and inhibits production of inflammatory mediators through a mechanism that, at least in part, involves inhibition of NF-kappaB activation.