S5a binds death receptor-6 to induce THP-1 monocytes differentiation via NF-κB pathway

Abstract

Analyses of supernatants from apoptotic cells have helped in the identification of many signals that modulate the states of cell activation and differentiation. However, the current knowledge about the soluble factors that are released during apoptosis is rather limited. Previous studies have shown that S5a and angiocidin (both encoded by PSMD4) induce human acute monocytic leukemia cells (THP-1 cells) to differentiate into macrophages, but the cell-surface receptor of S5a has not been identified. In this study, we show that apoptotic THP-1 cells release endogenous S5a that binds to death receptor-6 (DR6, also known as TNFRSF1), which was identified as an orphan receptor, to induce THP-1 cells to differentiate. Furthermore, we found that the NF-kB pathway is activated, and that the transcription factors WT1 (Wilms' tumor 1) and c-myb mediate S5a-induced THP-1 differentiation. We also show that differentiation is blocked by anti-DR6 antibody, DR6 siRNA, DR6-Fc, NF-kB inhibitor or WT1 siRNA treatment. Our findings indicate that the interaction between cells can determine their differentiation, and we provide evidence for a functional interaction between S5a and DR6, which provides a novel potential mechanism to induce the differentiation of cancer cells, especially during biotherapy for leukemia.

Death receptor 6 contributes to autoimmunity in lupus-prone mice

“…Moreover, although 25-1 Ab preferentially bound to CD3 + T cells, other cells binding 25-1 Ab were also observed in total splenocytes obtained from BWF1 mice. Several reports have shown DR6 expression on B cells, dendritic cells and macrophages194647. In addition, these cells are associated with GC reactions after immunization in healthy mice, as well as the disease progression of lupus-prone mice.…”

The Bioinformatic and Expression Analysis of PSMD4 Gene

“…Dukes' type C, colorectal adenocarcinoma cell line; LoVo, i.e. Colorectal Adenocarcinoma cells [11][12][13][14][15]. In our research, we want to show the expression profile of PSMD4 gene in different cancer cell lines and a normal cell.…”