Felli M P, Moschella C, Farina A R, Alesse E, Screpanti I, Teti D, Frati L, Gulino A
Department of Experimental Medicine, University of L'Aquila, Italy.
Cell Immunol. 1996 Sep 15;172(2):229-34. doi: 10.1006/cimm.1996.0237.
Prostaglandins, mainly those of the E series (PGE), are modulators of immune responses. Indeed PGE2 inhibits T cell activation and the transcription of the interleukin-2 (IL-2) gene, the major T cell growth factor. We observed that PGE2 inhibits IL-2 promoter transcription activity by interfering with signals activating the (-96 to -66 bp) octamer motif. This motif binds Oct-1 and Oct-2 as well as the phorbol ester and calcium ionophore-inducible jun and fos AP-1 factors. The PGE2-dependent down-modulation is observed in the presence of either the endogenous transacting factor Oct-1 or the exogenously expressed Oct-2. PGE2 does not regulate octamer function by influencing the jun and fos mRNA or Oct-1 protein levels or their DNA-binding abilities. Functional dissection of the octamer motif, through mutations of either the AP-1 or the octamer sites, revealed that the AP-1 site is dispensable for PGE2-dependent inhibition which instead may occur through the interference with the Oct-mediated transactivation of the octamer element. Our data suggest that the Oct-octamer interaction is a novel target of the PGE2-induced down-regulation of the IL-2 promoter.
前列腺素，主要是E系列（PGE）的前列腺素，是免疫反应的调节剂。事实上，PGE2抑制T细胞活化以及白细胞介素-2（IL-2）基因的转录，IL-2是主要的T细胞生长因子。我们观察到PGE2通过干扰激活（-96至-66 bp）八聚体基序的信号来抑制IL-2启动子转录活性。该基序结合Oct-1和Oct-2以及佛波酯和钙离子载体诱导的jun和fos AP-1因子。在存在内源性反式作用因子Oct-1或外源性表达的Oct-2的情况下，均可观察到PGE2依赖性下调。PGE2不会通过影响jun和fos mRNA或Oct-1蛋白水平或它们的DNA结合能力来调节八聚体功能。通过对AP-1或八聚体位点进行突变对八聚体基序进行功能剖析，结果显示AP-1位点对于PGE2依赖性抑制是可有可无的，相反，这种抑制可能是通过干扰Oct介导的八聚体元件反式激活而发生的。我们的数据表明，Oct-八聚体相互作用是PGE2诱导的IL-2启动子下调的新靶点。
