Phosphatidic acid induces the differentiation of human acute promyelocytic leukemic cells into dendritic cell‐like

Abstract

We investigated whether phosphatidic acid (PA) can differentiate the promyelocytic leukemia (PML)-retinoic acid receptor a (RARa)-expressing acute promyelocytic leukemic cell line, NB4, to dendritic cell (DC)-like cells. Dioctanoyl-PA alone upregulated the expression of DC markers. The expression of DC markers on NB4 cells was potentiated by the overexpression of phospholipase D and upregulation was blocked by the addition of n-butanol, an inhibitor of PA production. The expression of CD11c, CD83, and CCR7 in PA-treated NB4 cells was further increased by tumor necrosis factor (TNF)-a treatment. Increased functional capacities were also found in PA-differentiated and TNF-aactivated NB4 cells with respect to changes in T-cell proliferation, cytokine production, endocytic activity, and cytolytic capacity against undifferentiated NB4 cells. PA alone increased the phosphorylation of extracellular signal-regulated kinase (ERK)-1/2. The expression of DC markers was downregulated by PD98059, a specific inhibitor of ERK kinase or transient transfection of mutant-ERK. The level of PML-RARa fusion protein was decreased by PA treatment and PD98059 blocked the decrease of PML-RARa. These results suggest that PA induces differentiation of NB4 cells into DC-like cells and that the upregulation of antigen presenting cell markers is mediated by the activation of ERK and the downregulation of PML-RARa levels.

Characterization of α‐synuclein N‐terminal domain as a novel cellular phosphatidic acid sensor

“…Phosphatidic acid (PA) is the simplest phospholipid existing in biological membranes. Although PA constitutes only a minor fraction of total cell lipids, it is involved in the regulation of a wide variety of biological phenomena, including mitogenesis , migration , and differentiation . Many reports have demonstrated that PA controls a number of signaling proteins, such as phosphatidylinositol (PI)‐4‐phosphate 5‐kinase (PIP5K) , mammalian target of rapamycin , atypical protein kinase C , and p21 activated protein kinase 1 .…”

Dioleoyl‐phosphatidic acid selectively binds to α‐synuclein and strongly induces its aggregation

“…Phosphatidic acid (PA) is a plasma membrane phospholipid and acts as a second messenger to regulate a wide variety of cellular events . PA consists of various molecular species that have different acyl chains at the sn ‐1 and sn ‐2 positions, and consequently, mammalian cells contain at least 50 structurally distinct PA species.…”

The characterization and role of leukemia cell-derived dendritic cells in immunotherapy for leukemic diseases

“…The expression of CD11c, CD83, and CCR7 in PA-treated NB4 cells was further increased by TNF-α treatment. These results suggest that PA induces differentiation of NB4 cells into DC-like cells and that the upregulation of antigen-presenting cell markers is mediated by the activation of ERK and the downregulation of PML-RAR alpha levels (71).…”