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Antiparasitic and antiproliferative effects of indoleamine 2,3-dioxygenase enzyme expression in human fibroblasts.

机译:吲哚胺2,3-二加氧酶在人成纤维细胞中的表达具有抗寄生虫和抗增殖作用。

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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+ or 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 Cd(2+)-induced INDO activity also inhibited thymidine incorporation and led to cytotoxicity in INDO +ve 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.
机译:进行了研究,以评估吲哚胺2,3-二加氧酶(INDO)诱导在人成纤维细胞中γ干扰素(IFN-γ)的抗微生物和抗增殖作用中的作用。将INDO cDNA编码区克隆到pMEP4表达载体中,该载体包含有义(+ ve)或反义(-ve)方向的金属硫蛋白(MTII)启动子。用CdCl2或ZnSO4处理后,用有义构建体稳定转染的人成纤维细胞(GM637)表达了INDO活性,而用反义构建体转染的细胞则没有。用Cd2 +或Zn2 +处理后,鹦鹉热衣原体的生长在INDO + ve细胞中受到强烈抑制,但在INDO -ve细胞中没有受到抑制。该抑制与诱导的INDO活性水平相关,并且可以通过向培养基中添加过量的色氨酸来逆转。用Cd2 +处理后,弓形虫的生长在INDO + ve细胞中也受到强烈抑制,但在INDO -ve细胞中没有受到抑制。 Cd(2+)诱导的INDO活性的表达也抑制了胸腺嘧啶核苷的掺入并导致INDO + ve细胞而不是INDO -ve细胞的细胞毒性。因此,IFN-γ对INDO活性的诱导可能是IFN-γ对人成纤维细胞的抗微生物和抗增殖作用的重要因素。

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