Regulation of IL-1 and TNF-alpha expression during the differentiation of bone marrow derived macrophage.
Regulation of IL-1 and TNF-alpha expression during the differentiation of bone marrow derived macrophage.
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DOI：
10.4049/jimmunol.142.1.153
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发表时间：
1989-01
影响因子：
4.4
通讯作者：
Michael J. Myers;Jeffrey K. Pullen;Namit Ghildyal;E. Eustis-Turf;Lawrence B. Schook
中科院分区：
文献类型：
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作者：
Michael J. Myers;Jeffrey K. Pullen;Namit Ghildyal;E. Eustis-Turf;Lawrence B. Schook
巨噬细胞分化伴随着获得Ag呈递和杀肿瘤活性。在这组实验中，发现骨髓源性巨噬细胞（BMDM）的IL-1表达受到高度调节，IL-1 mRNA和mIL-1的表达仅出现在活化的离散阶段。IL-1 α（膜）mRNA的积累是由内毒素诱导的，而不是IFN-γ或CSF-1。仅在体外分化7天后，BMDM上的D10.G4.1 T细胞才检测到mIL-1。在培养第3天检测到分泌的IL-1 β，在用内毒素活化后观察到产生增强。发现IL-1 β mRNA在培养的第3天就在BMDM中组成型表达。内毒素作用30 min后，IL-1 β mRNA表达上调，2 ~ 6 h表达最高。未检测到IL-1 α mRNA的组成型表达，但内毒素暴露1小时导致IL-1 α转录物的出现。与IL-1 β一样，TNF-α mRNA也在分化的较长时间内组成性表达;然而，与IL-1 β相反，TNF-α mRNA的表达受内毒素和IFN-γ的上调。BMDM诱导的TNF-α巨噬细胞表达与肿瘤杀伤活性的获得相一致。编码原癌基因c-myc和c-fms的mRNA序列的检查表明c-myc仅在第3天表达，而c-fms在整个培养期间组成型表达。BMDM的内毒素刺激仅在培养的第3天导致c-myc表达的短暂增加，而内毒素对c-fms表达没有影响，直到培养的第7天，此时表达下降。与此相反，转铁蛋白受体mRNA转录本的表达，这也是在整个培养期间组成型表达，不受内毒素或IFN-γ的刺激。这些结果表明，在独特的“分化特异性”发育阶段，效应分子IL-1 α和β以及效应分子TNF-α的BMDM表达分别受到调节。
Macrophage differentiation is accompanied by the acquisition of both Ag presentation and tumoricidal activities. In this set of experiments, the expression of IL-1 by bone marrow-derived macrophage (BMDM) was found to be highly regulated, with both the expression of IL-1 mRNA and mIL-1 appearing only at discrete stages of activation. The accumulation of IL-1 alpha (membrane) mRNA was induced by endotoxin but not IFN-gamma or CSF-1. mIL-1 was detected by D10.G4.1 T cells on BMDM only after 7 days of in vitro differentiation. Secreted IL-1 beta was detected by day 3 of culture, with enhanced production observed after activation with endotoxin. IL-1 beta mRNA was found to be constitutively expressed in BMDM as early as day 3 of culture. The expression of IL-1 beta mRNA was up-regulated by endotoxin after 30 min of exposure with maximal expression occurring after 2 to 6 h of exposure. Constitutive expression of IL-1 alpha mRNA was not detected but 1 h of endotoxin exposure resulted in the appearance of IL-1 alpha transcripts. As with IL-1 beta, TNF-alpha mRNA was also constitutively expressed during a wide time period of differentiation; however, in contrast, to IL-1 beta, TNF-alpha mRNA expression was up-regulated by both endotoxin and IFN-gamma. The expression of TNF-alpha macrophage by BMDM coincided with the acquisition of tumoricidal activity. An examination of the mRNA sequences encoding the proto-oncogenes c-myc and c-fms demonstrated the expression of c-myc only on day 3, whereas c-fms was constitutively expressed throughout the culture period. Endotoxin stimulation of BMDM resulted in a transitory increase in c-myc expression only at day 3 of culture, whereas endotoxin had no effect on c-fms expression until 7 days of culture at which time expression declined. In contrast, the expression of transferrin receptor mRNA transcripts, which were also constitutively expressed throughout the entire culture period, were not affected by stimulation with either endotoxin or IFN-gamma. These results indicate BMDM expression of the affector molecules IL-1 alpha and beta and the effector molecule TNF-alpha are regulated separately during unique "differentiation-specific" phases of development.