Phosphatidic acid and tumor necrosis factor-alpha induce the expression of CD83 through mitogen activated protein kinase pathway in a CD34+ hematopoietic progenitor cell line, KG1.

To elucidate the signaling pathways involved in the expression of CD83, which is linked to the differentiation and maturation states of dendritic cells, we examined the effect of phosphatidic acid (PA) on the expression of CD83 in KG1, a CD34(+) hematopoietic progenitor cell. In the presence of tumor necrosis factor (TNF)-alpha, PA but not lyso-PA up-regulated CD83 on KG1 cells. Moreover, PA and TNF-alpha-induced expression of CD83 was slightly increased by propranolol, an inhibitor of PA phosphohydrolase but was unaffected by phospholipase A2 inhibitor. PA and TNF-alpha increased the phosphorylation of extracellular signal-regulated kinase (ERK)-1/2, p38-kinase, and c-Jun N-terminal kinase (JNK) by Western blotting. However, the up-regulation of CD83 by PA/TNF-alpha on KG1 was significantly abrogated by PD98059, a specific inhibitor of ERK kinase, but was enhanced by SP600125, a JNK inhibitor. Bis-indolylmaleimide, an inhibitor of protein kinase C, partially blocked the up-regulation of CD83 and ERK phosphorylation induced by PA and TNF-alpha. Moreover, the incubation of KG1 cells with phorbol ester and TNF-alpha for 5 days increased the protein level of phospholipase D. These results suggest that PA and TNF-alpha induce the up-regulation of CD83 and that their action is regulated by ERK and JNK.