Herbein G, Keshav S, Collin M, Montaner L J, Gordon S
Sir William Dunn School of Pathology, University of Oxford, UK.
Clin Exp Immunol. 1994 Mar;95(3):442-9. doi: 10.1111/j.1365-2249.1994.tb07016.x.
Cytokines such as tumour necrosis factor-alpha (TNF-alpha) and IL-1 beta may play a role in immunopathogenesis of AIDS. We studied early effects (0.5-48 h) of monocytotropic (ADA) or lymphotropic (IIIB) strains of HIV-1 on TNF-alpha and IL-1 beta mRNA expression in primary human macrophages by a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Three-day-old monocyte-derived macrophages were exposed either to tissue culture supernatants containing virus (at multiplicity of infection (m.o.i.) of 0.05) or to control supernatants free of virions and gp120. ADA strain, but not IIIB, replicated in primary tissue culture-differentiated macrophages (TCDM). Soluble CD4 (sCD4) was used to inhibit binding of both strains to macrophages. We found that TNF-alpha and IL-1 beta gene expression was induced by both strains 0.5-3 h after addition of virus, and that enhanced expression of both cytokines was inhibited by sCD4. We conclude that CD4-dependent binding to the cell surface is sufficient to enhance TNF-alpha and IL-1 beta mRNA, whereas productive viral replication in primary human macrophages is not required. Therefore, similar pathways regulate gene expression of TNF-alpha and IL-1 beta by macrophages during initial infection by HIV-1 in vitro.
细胞因子如肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）可能在艾滋病的免疫发病机制中起作用。我们通过半定量逆转录聚合酶链反应（RT-PCR）分析，研究了HIV-1的嗜单核细胞株（ADA）或嗜淋巴细胞株（IIIB）对原代人巨噬细胞中TNF-α和IL-1β mRNA表达的早期影响（0.5 - 48小时）。将培养三天的单核细胞衍生巨噬细胞暴露于含有病毒的组织培养上清液（感染复数（m.o.i.）为0.05）或不含病毒颗粒和gp120的对照上清液中。ADA株而非IIIB株在原代组织培养分化的巨噬细胞（TCDM）中复制。可溶性CD4（sCD4）用于抑制两种病毒株与巨噬细胞的结合。我们发现，在加入病毒后0.5 - 3小时，两种病毒株均可诱导TNF-α和IL-1β基因表达，且sCD4可抑制两种细胞因子表达的增强。我们得出结论，依赖CD4与细胞表面的结合足以增强TNF-α和IL-1β mRNA的表达，而原代人巨噬细胞中的病毒有效复制并非必需。因此，在体外HIV-1初始感染期间，巨噬细胞对TNF-α和IL-1β基因表达的调控途径相似。
