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 alpha (RAR alpha)-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-RAR alpha fusion protein was decreased by PA treatment and PD98059 blocked the decrease of PML-RAR alpha. 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.

• Authors: Jun-O Jin, Hae-Young Park, Ja-Woong Kim, Joo-In Park, Young-Seoub Hong, Do Sik Min, Jong-Young Kwak
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 100 Issue 1 Pg. 191-203 (Jan 01 2007) ISSN: 0730-2312 [Print] United States
• PMID: 16924673 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2006 Wiley-Liss, Inc.

Chemical References

• Biomarkers
• Cytokines
• Flavonoids
• Oncogene Proteins, Fusion
• Phosphatidic Acids
• promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
• dioctanoylphosphatidic acid
• Extracellular Signal-Regulated MAP Kinases
• Phospholipase D
• 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Topics

• Biomarkers (metabolism)
• Cell Differentiation (physiology)
• Cytokines (biosynthesis)
• Dendritic Cells (immunology, metabolism, pathology)
• Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors, metabolism)
• Flavonoids (pharmacology)
• Humans
• Leukemia, Promyelocytic, Acute (immunology, pathology)
• Oncogene Proteins, Fusion (metabolism)
• Phagocytosis
• Phosphatidic Acids (pharmacology, physiology)
• Phospholipase D (metabolism)
• Phosphorylation
• T-Lymphocytes (immunology, pathology)