A proliferation-inducing ligand (APRIL) is a member of the tumor necrosis factor superfamily that was first identified as a factor favoring tumorigenesis. APRIL is important fitness and survival factors for B cells and plasma cells in the periphery. Considering this, as well as the quantitative predominance of neutrophils among the peripheral blood leukocytes, we carried out the first study assessing the influence of the transforming growth factor (TGF)-β signaling pathway on APRIL expression in these cells. Furthermore, as the Rb1 ginsenoside is known to exhibit multiple pharmacological activities, we verified if the saponin is capable of modulating the process. The present study shows that TGF-β increased the expression of APRIL and the level of phospho-p38, phospho-Akt(T308), and phospho-Akt(S473) in the cytoplasmic fraction, as well as the expression of Fra1, c-Fos, and c-Jun in the nuclear fraction, of neutrophils. However, exposure of these cells to Rb1 reduced the expression and level of the investigated proteins. No changes were found in the expression of APRIL and the level of p-p38 in the cytoplasmic fraction of neutrophils following the application of Rb1 alone, as well as in the neutrophils incubated first with Rb1 and then with TGF-β, whereas a higher level of phosphorylation was observed for Akt and PI3 kinases in the cells. Moreover, a higher expression of all the studied transcription factors was observed in the nuclear fraction of neutrophils. Based on the observed changes, it may be assumed that the expression of APRIL molecule in TGF-β-induced neutrophils and its regulation by Rb1 are associated with PI3K/AKT signaling pathways and transcription factors Fra-1, Fra-2, c-Jun, and c-Fos. Rb1 appears to be a favorable factor that may be potentially used in the modulation of tumor-promoting APRIL expression.

诱导增殖的配体（APRIL）是肿瘤坏死因子超家族的成员，该家族最早被鉴定为有利于肿瘤发生的因子。APRIL是外周B细胞和浆细胞的重要适应性和生存因子。考虑到这一点，以及嗜中性粒细胞在外周血白细胞中的数量优势，我们进行了第一个评估转化生长因子（TGF）-β信号通路对这些细胞中APRIL表达的影响的研究。此外，由于已知人参Rb1具有多种药理活性，因此我们验证了皂苷是否能够调节该过程。目前的研究表明，TGF-β可增加APRIL的表达以及细胞质级分中的磷酸化p38，磷酸化Akt（T308）和磷酸化Akt（S473）的水平，以及中性粒细胞核部分中Fra1，c-Fos和c-Jun的表达。但是，这些细胞暴露于Rb1会降低所研究蛋白质的表达和水平。单独应用Rb1后，嗜中性粒细胞胞浆级分中APRIL的表达和p-p38水平没有变化，以及先与Rb1然后与TGF-β孵育的中性粒细胞均无变化观察到细胞中Akt和PI3激酶的磷酸化水平。此外，在嗜中性粒细胞的核部分中观察到所有研究的转录因子的更高表达。根据观察到的变化，可以假定，APRIL分子在TGF-β诱导的中性粒细胞中的表达及其受Rb1的调节与PI3K / AKT信号通路和转录因子Fra-1，Fra-2，c-Jun和c-Fos有关。Rb1似乎是一个可能在调节促肿瘤APRIL表达中潜在使用的有利因素。