ANTIPARASITIC AND ANTIPROLIFERATIVE EFFECTS OF INDOLEAMINE 2,3-DIOXYGENASE ENZYME EXPRESSION IN HUMAN FIBROBLASTS
ANTIPARASITIC AND ANTIPROLIFERATIVE EFFECTS OF INDOLEAMINE 2,3-DIOXYGENASE ENZYME EXPRESSION IN HUMAN FIBROBLASTS
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DOI：
10.1128/iai.62.6.2277-2284.1994
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发表时间：
1994-06-01
影响因子：
3.1
通讯作者：
MURPHY, MJ
中科院分区：
文献类型：
--
作者：
GUPTA, SL;CARLIN, JM;MURPHY, MJ
进行研究以评估吲哚胺2，3-双加氧酶（INDO）诱导在γ干扰素（IFN-γ）在人成纤维细胞中的抗微生物和抗增殖作用中的拟议作用。将INDO cDNA编码区克隆到pMEP 4表达载体中，所述表达载体以正义（+ve）或反义（-ve）方向含有金属硫蛋白（MTII）启动子。人成纤维细胞（GM 637）稳定转染正义结构表达INDO活性后，用氯化镉或硫酸锌处理，但细胞转染反义结构没有。用Cd ~（2+）、dr ~（2+）、Zn ~（2+）处理后，鹦鹉热衣原体在INDO ~+ve细胞中的生长受到强烈抑制，而在INDO ~-ve细胞中则没有。这种抑制作用与诱导的INDO活性水平相关，并且可以通过向培养基中加入过量的色氨酸来逆转。经Cd ~（2+）处理后，弓形虫在INDO ~+ve细胞中的生长也受到强烈抑制，而在INDO ~-ve细胞中则无此作用。表达Cd ~（2+）诱导的INDO活性也抑制胸苷掺入，并导致INDO Ct e细胞的细胞毒性，但不影响INDO -ve细胞。因此，IFN-γ诱导INDO活性可能是IFN-γ在人成纤维细胞中的抗微生物和抗增殖作用的重要因素。
Studies were carried out to evaluate the proposed role of indoleamine 2,3-dioxygenase (INDO) induction in the antimicrobial and antiproliferative effects of gamma interferon (IFN-gamma) in human fibroblasts. The INDO cDNA coding region was cloned in the pMEP4 expression Vector, containing the metallothionein (MTII) promoter in the sense (+ve) or the antisense (-ve) orientation. Human fibroblasts (GM637) stably transfected with the sense construct expressed INDO activity after treatment with CdCl2 or ZnSO4, but cells transfected with the antisense construct did not. The growth of Chlamydia psittaci was strongly inhibited in INDO +ve cells but not in INDO -ve cells after treatment with Cd2+ dr Zn2+. The inhibition correlated with the level of INDO activity induced and could be reversed by the addition of excess tryptophan to the medium. The growth of Toxoplasma gondii was also strongly inhibited in INDO +ve cells but not in INDO -ve cells after treatment with Cd2+. Expression of Cd2+-induced INDO activity also inhibited thymidine incorporation and led to cytotoxicity in INDO Ct e cells but not in INDO -ve cells. Thus, the induction of INDO activity by IFN-gamma may be an important factor in the antimicrobial and antiproliferative effects of IFN-gamma in human fibroblasts.