Sharma V, Xu M, Ritter L M, Wilkie N M
Department of Biology, University of West Florida, Pensacola 32514, USA.
Biochem Biophys Res Commun. 1996 Jun 25;223(3):526-33. doi: 10.1006/bbrc.1996.0928.
MIP-1 alpha is a secreted chemokine which can inhibit hematopoietic stem cells and modulate inflammatory responses. It is also an inhibitor of HIV replication in CD8+ T-cells. The expression of MIP-1 alpha is induced during cellular activation of CD4+ T-cells and monocytes. It is also expressed in transformed B-cells. We have previously identified a new transcription factor family (the MNP family) whose expression is crucial for the induction of MIP-1 alpha transcription during cellular activation and in transformed B cells. Monocytes and transformed B-cells normally express MNP-1 strongly and MNP-2 weakly, while T-cells strongly express only MNP-2. Recently, we reported that HIV-1 tat downregulates MIP-1 alpha expression in Jurkat T-cells. In this report we show induction of MNP-1 in Jurkat T-cells expressing HIV-1 tat. Expression of neither HTLV-1 tax in Jurkat T-cells nor EBV in B-cells had any effect on MNP-1 or MNP-2 expression, showing that the effect is specific for HIV-1 tat. We propose that HIV-1 tat may inhibit MIP-1 alpha expression by inducing MNP-1 expression in T-cells, probably by either competing with MNP-2 for binding to the MIP-1 alpha promoter or by sequestering it into inactive forms.
巨噬细胞炎性蛋白-1α（MIP-1α）是一种分泌型趋化因子，可抑制造血干细胞并调节炎症反应。它也是CD8 + T细胞中HIV复制的抑制剂。MIP-1α的表达在CD4 + T细胞和单核细胞的细胞活化过程中被诱导。它也在转化的B细胞中表达。我们之前鉴定了一个新的转录因子家族（MNP家族），其表达对于细胞活化期间以及转化的B细胞中MIP-1α转录的诱导至关重要。单核细胞和转化的B细胞通常强烈表达MNP-1，弱表达MNP-2，而T细胞仅强烈表达MNP-2。最近，我们报道HIV-1反式激活因子（tat）下调Jurkat T细胞中MIP-1α的表达。在本报告中，我们展示了在表达HIV-1 tat的Jurkat T细胞中MNP-1的诱导。Jurkat T细胞中HTLV-1 Tax的表达或B细胞中EBV的表达对MNP-1或MNP-2的表达均无任何影响，表明该效应对HIV-1 tat具有特异性。我们提出，HIV-1 tat可能通过在T细胞中诱导MNP-1表达来抑制MIP-1α表达，可能是通过与MNP-2竞争结合MIP-1α启动子或通过将其隔离成无活性形式。
