Poli G, Kinter A, Justement J S, Kehrl J H, Bressler P, Stanley S, Fauci A S
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1990 Jan;87(2):782-5. doi: 10.1073/pnas.87.2.782.
Tumor necrosis factor alpha (TNF-alpha) is an immunoregulatory cytokine capable of inducing viral expression in cells chronically infected with the human immunodeficiency virus (HIV), such as the promonocytic line U1 and the T-lymphocytic line ACH-2. In the present study, we demonstrate an autocrine mechanism of TNF-alpha-mediated HIV induction. Stimulation of U1 and ACH-2 cells with phorbol 12-myristate 13-acetate (PMA) resulted in the induction of TNF-alpha mRNA and the secretion of TNF-alpha. Of note is the fact that anti-TNF-alpha antibodies significantly suppressed the expression of HIV in PMA-stimulated U1 and ACH-2 cells. Furthermore, anti-TNF-alpha antibodies also suppressed both the constitutive and inducible levels of viral expression in the chronically infected promonocytic clone U33.3. This study illustrates the interrelationship between the regulation of HIV expression and normal immunoregulatory mechanisms in that virus expression, both constitutive and induced, can be modulated by an autocrine pathway involving TNF-alpha, a cytokine involved in the complex network of regulation of the normal human immune response.
肿瘤坏死因子α（TNF-α）是一种免疫调节细胞因子，能够在慢性感染人类免疫缺陷病毒（HIV）的细胞中诱导病毒表达，如原单核细胞系U1和T淋巴细胞系ACH-2。在本研究中，我们证明了TNF-α介导的HIV诱导的自分泌机制。用佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）刺激U1和ACH-2细胞导致TNF-α mRNA的诱导和TNF-α的分泌。值得注意的是，抗TNF-α抗体显著抑制了PMA刺激的U1和ACH-2细胞中HIV的表达。此外，抗TNF-α抗体也抑制了慢性感染的原单核细胞克隆U33.3中病毒表达的组成型和诱导型水平。这项研究说明了HIV表达调控与正常免疫调节机制之间的相互关系，即组成型和诱导型病毒表达均可通过涉及TNF-α的自分泌途径进行调节，TNF-α是参与正常人类免疫反应复杂调节网络的一种细胞因子。
