Phosphatidic acid induces the differentiation of human acute promyelocytic leukemic cells into dendritic cell-like.
We investigated whether phosphatidic acid (PA) can differentiate the promyelocytic leukemia (PML)-retinoic acid receptor alpha (RARalpha)-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)-alpha treatment. Increased functional capacities were also found in PA-differentiated and TNF-alpha-activated 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-RARalpha fusion protein was decreased by PA treatment and PD98059 blocked the decrease of PML-RARalpha. 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-RARalpha levels. J. Cell. Biochem. 100: 191-203, 2007. (c) 2006 Wiley-Liss, Inc.[1]References
- Phosphatidic acid induces the differentiation of human acute promyelocytic leukemic cells into dendritic cell-like. Jin, J.O., Park, H.Y., Kim, J.W., Park, J.I., Hong, Y.S., Min, d.o. .S., Kwak, J.Y. J. Cell. Biochem. (2007) [Pubmed]
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