Naif H M, Li S, Ho-Shon M, Mathijs J M, Williamson P, Cunningham A L
Westmead Institutes of Health Research, National Centre for HIV Virology Reearch, University of Sydney, Australia.
J Immunol. 1997 Jan 1;158(1):501-11.
The molecular mechanisms of the effects of IL-4 and IL-13 on HIV infection in human monocytes as they matured into monocyte-derived macrophages over 7 days were investigated using HIV-1(BaL), and low passage clinical strains. IL-4 and IL-13 up-regulated the expression of both genomic and spliced HIV mRNA in monocytes cultured on Teflon, as determined by Northern analysis and p24 Ag assay. Using a nuclear run-on assay, IL-4 stimulation was shown to enhance transcription by two- to threefold. IL-4 stimulated nuclear factor-kappaB nuclear translocation and binding before enhancement of HIV RNA expression. Conversely, IL-4 and IL-13 markedly and significantly inhibited HIV replication at the transcriptional level in monocyte-derived macrophages, and this occurred whether these cytokines were added before or after HIV infection. The reversal from stimulation to inhibition occurred after 3 to 5 days of adherence to plastic. IL-4 had no significant effect on HIV reverse transcription. The effect of both cytokines on the monocyte maturation/differentiation (CD11b, CD13, and CD26) and other macrophage markers (CD14 and CD68) was examined. IL-4 enhanced CD11b, but inhibited CD26 expression and delayed CD13 loss. IL-13 had similar effects on CD11b and CD13, but no effect on CD26. Hence, these cytokines do not simply enhance monocyte differentiation, but have complex and slightly divergent effects that impact on HIV replication probably through cell signaling pathways and nuclear factor-kappaB translocation.
利用HIV-1（BaL）和低传代临床毒株，研究了白细胞介素-4（IL-4）和白细胞介素-13（IL-13）在人单核细胞成熟为单核细胞衍生巨噬细胞的7天过程中对HIV感染的影响的分子机制。通过Northern分析和p24抗原检测确定，IL-4和IL-13上调了在聚四氟乙烯上培养的单核细胞中基因组和剪接的HIV mRNA的表达。使用核转录分析表明，IL-4刺激可使转录增强两到三倍。在HIV RNA表达增强之前，IL-4刺激核因子-κB的核转位和结合。相反，IL-4和IL-13在单核细胞衍生巨噬细胞的转录水平上显著抑制HIV复制，无论这些细胞因子是在HIV感染之前还是之后添加均如此。在贴壁到塑料上3至5天后，出现了从刺激到抑制的逆转。IL-4对HIV逆转录没有显著影响。研究了这两种细胞因子对单核细胞成熟/分化（CD11b、CD13和CD26）以及其他巨噬细胞标志物（CD14和CD68）的影响。IL-4增强了CD11b的表达，但抑制了CD26的表达并延迟了CD13的丢失。IL-13对CD11b和CD13有类似影响，但对CD26没有影响。因此，这些细胞因子并非简单地增强单核细胞分化，而是具有复杂且略有不同的影响，可能通过细胞信号通路和核因子-κB转位影响HIV复制。
