C/EBP-BETA REGULATION OF THE TUMOR-NECROSIS-FACTOR-ALPHA GENE
C/EBP-BETA REGULATION OF THE TUMOR-NECROSIS-FACTOR-ALPHA GENE
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DOI：
10.1172/jci117482
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发表时间：
1994-10-01
影响因子：
15.9
通讯作者：
NESS, SA
中科院分区：
文献类型：
--
作者：
POPE, RM;LEUTZ, A;NESS, SA
活化的巨噬细胞通过分泌细胞因子和蛋白酶促进慢性炎症。肿瘤坏死因子α（TNF α）在此过程中特别重要，因为它能够以自分泌和旁分泌方式调节其他炎症介质。负责TNF α的细胞类型特异性调节的机制尚不清楚。我们目前的数据表明，TNF α的表达是由转录因子C/EBP β（NF-IL 6）调节。在共转染试验中，C/EBP β激活TNF α基因启动子，并在不能结合密切相关的蛋白C/EBP α的位点与其结合。最后，C/EBP β的显性阴性版本阻断了髓系细胞中TNF α启动子的激活。我们的研究结果暗示C/EBP β是髓单核细胞对TNF α的重要调节因子。
Activated macrophages contribute to chronic inflammation by the secretion of cytokines and proteinases. Tumor necrosis factor alpha (TNF alpha) is particularly important in this process because of its ability to regulate other inflammatory mediators in an autocrine and paracrine fashion. The mechanism(s) responsible for the cell type-specific regulation of TNF alpha is not known. We present data to show that the expression of TNF alpha is regulated by the transcription factor C/EBP beta (NF-IL6). C/EBP beta activated the TNF alpha gene promoter in cotransfection assays and bound to it at a site which failed to bind the closely related protein C/EBP alpha. Finally, a dominant-negative version of C/EBP beta blocked TNF alpha promoter activation in myeloid cells. Our results implicate C/EBP beta as an important regulator of TNF alpha by myelomonocytic cells.