INDUCTION OF TRYPTOPHAN CATABOLISM IS THE MECHANISM FOR GAMMA-INTERFERON-MEDIATED INHIBITION OF INTRACELLULAR CHLAMYDIA-PSITTACI REPLICATION IN T24 CELLS
INDUCTION OF TRYPTOPHAN CATABOLISM IS THE MECHANISM FOR GAMMA-INTERFERON-MEDIATED INHIBITION OF INTRACELLULAR CHLAMYDIA-PSITTACI REPLICATION IN T24 CELLS
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DOI：
10.1128/iai.53.2.347-351.1986
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发表时间：
1986-08-01
影响因子：
3.1
通讯作者：
LANDRY, GJ
中科院分区：
文献类型：
--
作者：
BYRNE, GI;LEHMANN, LK;LANDRY, GJ
在各种浓度的人重组γ干扰素（Hu-rIFN-γ）存在下，将人泌尿上皮（T24）细胞孵育24小时。然后感染了鹦鹉热衣原体的6 BC菌株这导致与Hu-rIFN-γ浓度成比例的细胞内衣原体包涵体发展的减少。在感染后24小时通过光学显微镜检查Giemsa染色的细胞时存在。当将色氨酸加入Hu-rIFN-γ中时，在感染后立即处理细胞，逆转Hu-rIFN-γ-介导的抑制作用与加入的色氨酸浓度成比例地发生。添加异亮氨酸或赖氨酸均未导致抗衣原体状态逆转。发现L-[3 H]色氨酸向酸溶性细胞内库的转运在Hu-rIFN-γ中大大增强。处理的T24细胞与未处理的细胞测量的比率进行比较。[3 H]亮氨酸的运输在处理的细胞中没有增加。用Hu-rIFN-γ处理的细胞也将L-[3 H]色氨酸降解为催化剂，其与N-甲酰犬尿氨酸和犬尿氨酸共色谱，如通过高效液相色谱法测量的。我们推断Hu-rIFN-γ-介导的细胞内C.鹦鹉热在T24细胞中的复制通过消耗必需氨基酸色氨酸而发生，最可能是通过诱导吲哚胺-2，3-双加氧酶（色氨酸催化剂的起始酶）。
Human uroepithelial (T24) cells were incubated for 24 h in the presence of various concentrations of human recombinant gamma interferon (Hu-rIFN-.gamma.) and then infected with the 6BC strain of Chlamydia psittaci. This resulted in a reduction of intracellular chlamydial inclusion development in proportion into the concentration of Hu-rIFN-.gamma. present when Giemsa-stained cells were examined by light microscopy 24 h after infection. When tryptophan was added to Hu-rIFN-.gamma.-treated cells just after infection, reversal of the Hu-rIFN-.gamma.-mediated inhibition occurred in proportion to the concentration of tryptophan added. Addition of either isoleucine or lysine did not result in reversal of the antichlamydial state. Transport of L-[3H]tryptophan into acid-soluble intracellular pools was found to be greatly enhanced in Hu-rIFN-.gamma.-treated T24 cells compared with the rate measured for untreated cells. Transport of [3H]leucine was not increased in treated cells. Cells treated with Hu-rIFN-.gamma. also degraded L-[3H]tryptophan to catabolites that cochromatographed with N-formylkynurenine and kynurenine as measured by high-performance liquid chromatography. We conclude that Hu-rIFN-.gamma.-mediated inhibition of intracellular C. psittaci replication in T24 cells occurs by depletion of the essential amino acid tryptophan, most likely via the induction of indoleamine-2,3-dioxygenase, the initial enzyme of tryptophan catabolism.