4-Chloro-3-hydroxyanthranilate, 6-chlorotryptophan and norharmane attenuate quinolinic acid formation by interferon-gamma-stimulated monocytes (THP-1 cells).
4-Chloro-3-hydroxyanthranilate, 6-chlorotryptophan and norharmane attenuate quinolinic acid formation by interferon-gamma-stimulated monocytes (THP-1 cells).
复制标题
4-Chloro-3-羟基邻氨基苯甲酸、6-氯色氨酸和去甲哈马烷可减弱干扰素-γ刺激的单核细胞（THP-1 细胞）形成的喹啉酸。
作者：
Kuniaki Saito;Cai;Monica Masana;Jeffrey S. Crowley;Sanford P. Markey;M. Heyes
喹啉酸和L-犬尿氨酸的积累在免疫激活后发生在脑和/或血液中，并且可能来源于吲哚胺2，3-双加氧酶和其他犬尿氨酸途径酶诱导后的L-色氨酸。在本研究中，对来自脑或全身组织的各种细胞系的调查显示，虽然所有检查的细胞通过增加L-[13 C6]色氨酸转化为L-犬尿氨酸而对干扰素-γ产生反应，（人：B淋巴细胞、神经母细胞瘤、胶质母细胞瘤、肺、肝、肾;大鼠脑：小胶质细胞、星形胶质细胞和少突胶质细胞），仅巨噬细胞源性细胞（外周血单核细胞; THP-1，U-937）和某些肝细胞（SKHep 1）合成[13 C6]喹啉酸。肿瘤坏死因子-α增强干扰素-γ在THP-1细胞中的作用。去甲哈尔烷、6-氯-DL-色氨酸和4-氯-3-羟基邻氨基苯甲酸酯减弱THP-1细胞的喹啉酸形成，IC 50值分别为51 μ M、58 μ M和0.11 μ M。去甲哈尔烷和6-氯-DL-色氨酸减弱L-犬尿氨酸的形成，IC 50值分别为43 μ M和51 μ M，而4-氯-3-羟基邻氨基苯甲酸酯对L-犬尿氨酸的积累没有影响。L-犬尿氨酸和喹啉酸形成的减少与以下报道一致：去甲哈尔烷是吲哚胺2，3-双加氧酶的抑制剂，6-氯-DL-色氨酸通过犬尿氨酸途径代谢，4-氯-3-羟基邻氨基苯甲酸是3-羟基邻氨基苯甲酸3，4-双加氧酶的抑制剂。这些结果表明，许多组织可能有助于吲哚胺2，3-双加氧酶诱导和免疫激活后产生L-犬尿氨酸。在巨噬细胞和某些类型的肝细胞中，喹啉酸可以直接由L-色氨酸合成，尽管从血液中摄取喹啉酸前体可能有助于不能将L-犬尿氨酸转化为喹啉酸的细胞中的喹啉酸合成。
Accumulation of quinolinic acid and L-kynurenine occurs in the brain and/or blood following immune activation, and may derive from L-tryptophan following induction of indoleamine 2,3-dioxygenase and other kynurenine-pathway enzymes. In the present study a survey of various cell lines derived from either brain or systemic tissues showed that, while all cells examined responded to interferon-gamma by increased conversion of L-[13C6]tryptophan into L-kynurenine (human: B-lymphocytes, neuroblastoma, glioblastoma, lung, liver, kidney; rat brain: microglia, astrocytes and oligodendrocytes), only macrophage-derived cells (peripheral-blood mononuclear cells; THP-1, U-937) and certain liver cells (SKHep1) synthesized [13C6]quinolinic acid. Tumour necrosis factor-alpha enhanced the effects of interferon-gamma in THP-1 cells. Norharmane, 6-chloro-DL-tryptophan and 4-chloro-3-hydroxyanthranilate attenuated quinolinic acid formation by THP-1 cells with IC50 values of 51 microM, 58 microM and 0.11 microM respectively. Norharmane and 6-chloro-DL-tryptophan attenuated L-kynurenine formation with IC50 values of 43 microM and 51 microM respectively, whereas 4-chloro-3-hydroxyanthranilate had no effect on L-kynurenine accumulation. The reductions in L-kynurenine and quinolinic acid formation are consistent with the reports that norharmane is an inhibitor of indoleamine 2,3-dioxygenase, 6-chloro-DL-tryptophan is metabolized through the kynurenine pathway, and 4-chloro-3-hydroxyanthranilate is an inhibitor of 3-hydroxyanthranilate 3,4-dioxygenase. These results suggest that many tissues may contribute to the production of L-kynurenine following indoleamine 2,3-dioxygenase induction and immune activation. Quinolinic acid may be directly synthesized from L-tryptophan in both macrophages and certain types of liver cells, although uptake of quinolinic acid precursors from blood may contribute to quinolinic acid synthesis in cells that cannot convert L-kynurenine into quinolinic acid.
DOI：
10.1073/pnas.85.11.4079
发表时间：
1988-06-01
影响因子：
11.1
作者：
SCHWARCZ, R;OKUNO, E;WHETSELL, WO
通讯作者：
WHETSELL, WO