Minty A, Chalon P, Guillemot J C, Kaghad M, Liauzun P, Magazin M, Miloux B, Minty C, Ramond P, Vita N
Sanofi Elf Bio Recherches, Labège, France.
Eur Cytokine Netw. 1993 Mar-Apr;4(2):99-110.
We have isolated a cDNA (NC28) transcribed from a mRNA which is transiently induced in U937 promonocytic cells by PMA and super-induced by cycloheximide. NC28 cDNA encodes a new member of the chemokine family, MCP-3, recently purified from MG-63 osteosarcoma cells by Van Damme et al. [1]. The MCP-3 protein sequence shows 74% identity with human monocyte chemoattractant protein 1 (MCP-1) and, like MCP-1, recombinant MCP-3 protein shows chemotactic activity for monocytes but not for neutrophils. However the secreted MCP-3 protein differs from MCP-1 in being N-glycosylated. The 3' noncoding regions of MCP-3 and MCP-1 mRNAs are more diverged (44%), allowing specific cDNA probes to be made, and indicating that the two genes are evolutionarily distant. Sequence comparisons of the 3' noncoding regions suggest that MCP-3 may be the human homologue of the mouse MARC gene [2], and that MCP-1 and MCP-3 genes arose by a gene duplication event before the mammalian radiation. Both MCP-1 and MCP-3 mRNAs are expressed by PBMC, principally by monocytes, with MCP-1 mRNA being expressed at levels 2-4 times that of MCP-3 mRNA. However, while MCP-1 mRNA is also expressed at high levels in fibroblast or astrocytoma cell lines after IL-1 and TNF stimulation, MCP-3 mRNA is expressed only at very low levels in these cells. The cellular origin of MCP-3 is thus more restricted than that of MCP-1. In our experiments on PBMC, LPS is not a consistent inducer of MCP-1 and MCP-3 mRNAs. In some experiments, it actually decreases levels of these two mRNAs, while concomitantly increasing IL-6 and TNF-alpha mRNA levels. Levels of MCP-1 and MCP-3 mRNAs in PBMC are both increased by IFN-gamma, although IL-6 mRNA is not induced. They are also increased by PHA-P and are decreased, in most cases, by IL-13 [3]. MCP-1 and MCP-3 mRNAs are thus co-ordinately regulated in monocytes in response to a number of inducing or inhibitory agents, in a manner differing in several respects from that of other monokines such as IL-6.
我们分离出了一个由mRNA转录而来的cDNA（NC28），该mRNA在U937前单核细胞中被佛波酯（PMA）短暂诱导，并被环己酰亚胺超诱导。NC28 cDNA编码趋化因子家族的一个新成员——MCP - 3，它最近由范·达姆等人[1]从MG - 63骨肉瘤细胞中纯化得到。MCP - 3蛋白序列与人类单核细胞趋化蛋白1（MCP - 1）有74%的同源性，并且与MCP - 1一样，重组MCP - 3蛋白对单核细胞具有趋化活性，而对中性粒细胞没有趋化活性。然而，分泌的MCP - 3蛋白与MCP - 1的不同之处在于它是N - 糖基化的。MCP - 3和MCP - 1 mRNA的3'非编码区差异更大（44%），这使得可以制备特异性的cDNA探针，表明这两个基因在进化上距离较远。3'非编码区的序列比较表明，MCP - 3可能是小鼠MARC基因[2]的人类同源物，并且MCP - 1和MCP - 3基因是在哺乳动物辐射之前通过基因复制事件产生的。MCP - 1和MCP - 3 mRNA均由外周血单核细胞（PBMC）表达，主要由单核细胞表达，MCP - 1 mRNA的表达水平是MCP - 3 mRNA的2 - 4倍。然而，虽然在白细胞介素 - 1（IL - 1）和肿瘤坏死因子（TNF）刺激后，MCP - 1 mRNA在成纤维细胞或星形细胞瘤细胞系中也高水平表达，但MCP - 3 mRNA在这些细胞中仅以非常低的水平表达。因此，MCP - 3的细胞来源比MCP - 1更受限制。在我们对外周血单核细胞的实验中，脂多糖（LPS）并不是MCP - 1和MCP - 3 mRNA的一致诱导剂。在一些实验中，它实际上降低了这两种mRNA的水平，同时增加了IL - 6和TNF -α mRNA的水平。外周血单核细胞中MCP - 1和MCP - 3 mRNA的水平都因干扰素 -γ（IFN -γ）而增加，尽管IL - 6 mRNA未被诱导。它们也因植物血凝素 - P（PHA - P）而增加，并且在大多数情况下因IL - 13[3]而降低。因此，MCP - 1和MCP - 3 mRNA在单核细胞中对多种诱导或抑制因子的反应中受到协同调节，其方式在几个方面与其他单核因子如IL - 6不同。
