Transforming growth factor beta suppresses human immunodeficiency virus expression and replication in infected cells of the monocyte/macrophage lineage.
Transforming growth factor beta suppresses human immunodeficiency virus expression and replication in infected cells of the monocyte/macrophage lineage.
复制标题
DOI：
10.1084/jem.173.3.589
复制
发表时间：
1991-03-01
期刊：
影响因子：
--
通讯作者：
Fauci AS
中科院分区：
文献类型：
--
作者：
Poli G;Kinter AL;Justement JS;Bressler P;Kehrl JH;Fauci AS
多效性免疫调节细胞因子转化生长因子β（TGF-β）在慢性感染的前单核细胞系U1中有效抑制获得性免疫缺陷综合征的病原体人类免疫缺陷病毒（HIV）的产生。TGF-β显着（50-90%）抑制HIV逆转录酶的生产和合成的病毒蛋白在U1细胞刺激佛波醇肉豆蔻酸酯（PMA）或白细胞介素6（IL- 6）。此外，TGF-β抑制PMA诱导U1细胞中的HIV转录。相反，TGF-β对肿瘤坏死因子α（TNF-α）诱导的HIV表达无显著影响。这些抑制作用不是通过干扰素α（IFN-α）的诱导介导的。TGF-β还抑制HIV复制的主要单核细胞衍生的巨噬细胞感染体外，无论是在没有外源性细胞因子和IL-6刺激的文化。相反，在慢性感染的T细胞系（ACH-2）或体外感染的原代T细胞母细胞中均未观察到TGF-β的显著作用。因此，TGF-β可能在感染个体的感染单核细胞或组织巨噬细胞中作为HIV表达的负调节剂发挥潜在的重要作用。
The pleiotropic immunoregulatory cytokine transforming growth factor beta (TGF-beta) potently suppresses production of the human immunodeficiency virus (HIV), the causative agent of the acquired immunodeficiency syndrome, in the chronically infected promonocytic cell line U1. TGF-beta significantly (50-90%) inhibited HIV reverse transcriptase production and synthesis of viral proteins in U1 cells stimulated with phorbol myristate acetate (PMA) or interleukin 6 (IL- 6). Furthermore, TGF-beta suppressed PMA induction of HIV transcription in U1 cells. In contrast, TGF-beta did not significantly affect the expression of HIV induced by tumor necrosis factor alpha (TNF-alpha). These suppressive effects were not mediated via the induction of interferon alpha (IFN-alpha). TGF-beta also suppressed HIV replication in primary monocyte-derived macrophages infected in vitro, both in the absence of exogenous cytokines and in IL-6-stimulated cultures. In contrast, no significant effects of TGF-beta were observed in either a chronically infected T cell line (ACH-2) or in primary T cell blasts infected in vitro. Therefore, TGF-beta may play a potentially important role as a negative regulator of HIV expression in infected monocytes or tissue macrophages in infected individuals.