Brooks J W, Yoza B K, Mizel S B
Department of Microbiology and Immunology, Wake Forest University Medical Center, Winston-Salem, NC 27157, USA.
Mol Immunol. 1995 Aug;32(11):779-88. doi: 10.1016/0161-5890(95)00055-j.
We have examined the regulation of the AP-1 DNA transcription complex during T cell activation in response to interleukin 1 (IL-1) and phorbol ester (TPA) treatment of the IL-1 responsive murine thymoma T cell line, EL4 6.1 C 10. IL-1 synergistically enhances the stimulatory effect of TPA on AP-1-mediated gene expression in this cell line. To elucidate the mechanism(s) by which IL-1 enhances AP-1-mediated gene expression, we examined the effect of IL-1 on the synthesis and turnover of Jun B, the member of the jun gene family that is present in AP-1 complexes in EL4 cells. We found that IL-1 + TPA-treated cells contain significantly higher Jun B protein levels than cells treated with TPA alone. IL-1 promotes the prolonged accumulation of Jun B, whereas the cellular content of Jun B decreases dramatically after 6 hr in cells treated with only TPA. IL-1 enhancement of Jun B protein levels is not the result of a change in the turnover rate of the Jun B protein, but rather results from the maintenance of sufficient jun B mRNA to support continued accumulation of newly synthesized protein. In addition to Jun B, we found that the T cell AP-1 complex contains the Fra-1 protein, a member of the fos gene family. Although IL-1 dramatically increases Jun B accumulation, it does not enhance TPA-induced Fra-1 protein levels in EL4 cells. Thus, the stimulation of AP-1-mediated gene expression by IL-1 in EL4 cells is due to the promotion of Jun B protein accumulation that, in turn, facilitates Jun B heterodimerization with TPA-induced Fra-1 protein, thereby forming an active AP-1 complex.
我们研究了白细胞介素1（IL-1）应答性小鼠胸腺瘤T细胞系EL4 6.1 C 10在经白细胞介素1（IL-1）和佛波酯（TPA）处理激活T细胞过程中AP-1 DNA转录复合物的调控情况。在该细胞系中，IL-1协同增强了TPA对AP-1介导的基因表达的刺激作用。为阐明IL-1增强AP-1介导的基因表达的机制，我们研究了IL-1对Jun B合成和周转的影响，Jun B是jun基因家族的成员，存在于EL4细胞的AP-1复合物中。我们发现，经IL-1 + TPA处理的细胞中Jun B蛋白水平显著高于仅用TPA处理的细胞。IL-1促进Jun B的长期积累，而仅用TPA处理的细胞中，Jun B的细胞含量在6小时后会急剧下降。IL-1增强Jun B蛋白水平并非Jun B蛋白周转速率变化的结果，而是由于维持了足够的jun B mRNA以支持新合成蛋白的持续积累。除了Jun B，我们还发现T细胞AP-1复合物包含Fos基因家族成员Fra-1蛋白。尽管IL-1显著增加Jun B的积累，但它并未增强EL4细胞中TPA诱导的Fra-1蛋白水平。因此，IL-1在EL4细胞中对AP-1介导的基因表达的刺激作用是由于促进了Jun B蛋白的积累，进而促进了Jun B与TPA诱导的Fra-1蛋白的异源二聚化，从而形成活性AP-1复合物。
