Involvement of ERK and JNK pathways in IFN-γ-induced B7-DC expression on tumor cells.
OBJECTIVE
B7-DC on tumor cells was demonstrated to promote tumor immunity; however, the precise mechanism responsible for the aberrant B7-DC expression remains unknown. Interferon gamma (IFN-γ) can induce B7-DC expression on macrophages and has been shown to regulate anti-tumor immunity by various mechanisms. This study was designed to investigate the relationship of IFN-γ and B7-DC on tumor cells and further explored the signal transduction pathways involved.


METHODS
RT-PCR and flow cytometry were used for the analysis of B7-DC expression on various tumor cells. The phosphorylation of p38, ERK1/2, JNK, Akt, and JAK2 was determined by Western blot.


RESULTS
IFN-γ markedly up-regulated B7-DC expression on various tumor cells and resulted in the phosphorylation of JAK2, JNK, ERK, p38, and Akt. Inhibition of ERK or JNK pathway significantly decreased IFN-c-induced B7-DC expression, whereas inhibition of phosphorylation of Akt, p38, and JAK2 had very little effect on IFN-γ-induced B7-DC expression.


CONCLUSIONS
Our findings demonstrate that the pretreatment of tumor cells with IFN-γ enhances B7-DC expression through ERK and JNK pathways.
Deng
Junfang
J
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
Qian
Yigang
Y
Geng
Lei
L
Xie
Haiyang
H
Wang
Yan
Y
Jiang
Guoping
G
Zhou
Lin
L
Zhang
Ming
M
Zheng
Shusen
S
D000704:Analysis of Variance; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D010766:Phosphorylation; D061027:Programmed Cell Death 1 Ligand 2 Protein; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D018122:B7-1 Antigen; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein; D012333:RNA, Messenger; D007371:Interferon-gamma; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4
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