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

Abstract

Analyses of apoptotic cell supernatants have helped identify many signals that modulate the states of activation and differentiation in the congeneric or other cells. However, the current knowledge about these soluble factors that are released during apoptosis is rather limited. Previous studies have shown that S5a/Angiocidin induced human acute monocytic leukemia cells (THP-1 cells) to differentiation into macrophages, but the cell surface receptor of S5a has not been identified. In this study we show that apoptotic THP-1 cells released endogenous S5a, and S5a bound with death receptor-6, which was identified as an orphan receptor, to induce THP-1 cells differentiation. Furthermore, we found NF-κB pathway was activated and the transcription factor WT1 and c-myb mediated THP-1 differentiation induced by S5a. And we also show that the differentiation was blocked after anti-DR6 antibody, DR6 siRNA, DR6-Fc, NF-κB inhibitor, or WT1 siRNA treatment. Our finding indicated that the interaction between cells can determine their destination. And we provided evidence for a functional interaction between S5a and DR6, which provides a novel target that can induce the differentiation of cancer cells especially for biotherapy of leukemia.