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.
Keywords: APRIL; Ginsenoside Rb1; Neutrophils; PI3K/Akt; TGF-β; p38.