12-O-tetradecanoyl phorbol 13-acetate induces the expression of B7-DC, -H1, -H2, and -H3 in K562 cells
Jang, B-Churl.; Park, Y-Kyoung.; Choi, I-Hak.; Kim, S-Pyo.; Hwang, J-Bok.; Baek, W-Ki.; Suh, M-Ho.; Mun, K-Chul.; Suh, S-Il.
International Journal of Oncology 31(6): 1439-1447
2007
ISSN/ISBN: 1019-6439 PMID: 17982670 Document Number: 605881
Induction of the B7 family molecules by 12-O-tetradecanoyl phorbol 13-acetate (TPA) has been reported, however, the mechanism by which TPA up-regulates these molecules remains poorly understood. In this study, the expression of B7-DC, -H1, -H2, and -H3 in response to TPA was markedly induced in K562 cells. TPA also induced activation of ERK, p38 mitogen-activated protein kinase (MAPK), JNK, phosphatidylinositol-3-kinase (PI-3K), or nuclear factor (NF)-kappa B. Pre-treatments with protein kinase C (PKC) inhibitors significantly inhibited TPA-induced expression of B7-DC, -Hl, -H2, and -H3 mRNA as well as TPA-induced phosphorylation of ERK, p38 MAPK, JNK, and PI-3K. TPA-induced expression of B7-DC, -Hl, -H2, and -H3 mRNA was abrogated by pre-treatments with inhibitors of ERK and p38 MAPK. However, inhibition of PI-3K and JNK only caused decrease of TPA-induced B7-DC mRNA and B7-H3 mRNA, respectively. TPA-induced degradation of I kappa B-alpha was markedly abrogated by treatments with PKC inhibitors, but not by treatments with inhibitors of ERK, p38 MAPK, JNK, or PI-3K. NF-kappa B inhibitors significantly attenuated the expression of B7-DC, -H1, -H2, and -H3 mRNA in response to TPA. These results suggest that TPA induces the expression of B7-DC, -H1, -H2, and -H3 mRNA in K562 cells via activation of PKC, ERK, p38 MAPK, and NF-kappa B. Distinctly, the expression of B7-DC mRNA and -H3 mRNA in response to TPA is also PI-3K- and JNK-dependent, respectively.