12-O-tetradecanoyl phorbol 13-acetate induces the expression of B7-DC, -H1, -H2, and -H3 in K562 cells.
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)-kappaB. Pre-treatments with protein kinase C (PKC) inhibitors significantly inhibited TPA-induced expression of B7-DC, -H1, -H2, and -H3 mRNA as well as TPA-induced phosphorylation of ERK, p38 MAPK, JNK, and PI-3K. TPA-induced expression of B7-DC, -H1, -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 IkappaB-alpha was markedly abrogated by treatments with PKC inhibitors, but not by treatments with inhibitors of ERK, p38 MAPK, JNK, or PI-3K. NF-kappaB 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-kappaB. Distinctly, the expression of B7-DC mRNA and -H3 mRNA in response to TPA is also PI-3K- and JNK-dependent, respectively.
Jang
Byeong-Churl
BC
Chronic Disease Research Center and Institute for Medical Science, Keimyung University School of Medicine, Daegu, Korea.
Park
Yu-Kyoung
YK
Choi
In-Hak
IH
Kim
Sang-Pyo
SP
Hwang
Jin-Bok
JB
Baek
Won-Ki
WK
Suh
Min-Ho
MH
Mun
Kyu-Chul
KC
Suh
Seong-Il
SI
D015703:Antigens, CD / Q000235:genetics*; D060887:B7 Antigens; D018122:B7-1 Antigen / Q000235:genetics*; D060890:B7-H1 Antigen; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D060945:Inducible T-Cell Co-Stimulator Ligand; D020014:K562 Cells; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D061027:Programmed Cell Death 1 Ligand 2 Protein; D011493:Protein Kinase C / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D015703:Antigens, CD; D060887:B7 Antigens; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C423237:CD276 protein, human; C498514:ICOSLG protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein; D017382:Reactive Oxygen Species; D011971:Receptors, Immunologic; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate