Research Papers:

The potential mechanism of extracellular high mobility group box-1 protein mediated p53 expression in immune dysfunction of T lymphocytes

Ying-Yi Luan, Min Jia, Hui Zhang, Fu-Jun Zhu, Ning Dong, Yong-Wen Feng, Ming Wu, Ya-Lin Tong and Yong-Ming Yao _

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Oncotarget. 2017; 8:112959-112971. https://doi.org/10.18632/oncotarget.22913

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Ying-Yi Luan1,2,*, Min Jia1,2,*, Hui Zhang2, Fu-Jun Zhu1,2, Ning Dong2, Yong-Wen Feng3, Ming Wu3, Ya-Lin Tong1 and Yong-Ming Yao1,2,3

1Department of Burns and Plastic Surgery, The 181st Hospital of Chinese PLA, Guilin 541002, People’s Republic of China

2Trauma Research Center, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, People’s Republic of China

3Department of Critical Care Medicine, The Second People’s Hospital of Shenzhen, Shenzhen 518035, People’s Republic of China

*These authors have contributed equally to this work

Correspondence to:

Yong-Ming Yao, email: [email protected]

Ya-Lin Tong, email: [email protected]

Keywords: high mobility group box-1 protein; p53; p38 mitogen-activated protein kinase; T lymphocytes; immune dysfunction

Received: August 31, 2017    Accepted: November 23, 2017    Published: December 04, 2017


In the present study, we examined the activity of p53 protein in Jurkat cells treated with high mobility group box-1 protein (HMGB1), thereafter we investigated the mechanism of extracellular HMGB1 mediated p53 expression in immune dysfunction of T lymphocytes. mRNA expression of p53, mdm2, and p21 was determined by Real-time reverse transcription-polymerase chain reaction(RT-PCR). The apoptotic rate of Jurkat cells was analyzed by flow cytometry. Expressions of bcl-2, bax, caspase-3, phosphorylated (p) extracellular signal-regulated kinase (ERK)1/2, ERK1/2, p-p38 mitogen-activated protein kinase (MAPK), p38 MAPK, and p-c-jun amino-terminal kinase (JNK)1/2 and JNK1/2 were simultaneously determined by Western blotting. After treatment with HMGB1 (100 ng/ml or 1000 ng/ml), the proliferative activity of Jurkat cells was significantly decreased, and a low and medium concentration of HMGB1 induced an up-regulation of p53 mRNA, p-p53 and p53 protein expression. Meanwhile, levels of mdm2 and p21 were elevated by incubated with HMGB1 (100 ng/ml) for 24 or 48 hours. Moreover, the proliferation of Jurkat cells in response to HMGB1 (100 ng/ml) in the vector group was significantly depressed. The bax and caspase-3 levels in p53 shRNA-expressed cells treated with HMGB1 (100 ng/ml) was markedly decreased, whereas expression of bcl-2 was obviously enhanced. Among ERK1/2, p38 MAPK and JNK1/2 signaling, only p38 MAPK pathway could be significantly activated by treatment with HMGB1, and the specific inhibitor of p38 MAPK was used, p53 and p-p53 expression induced by HMGB1 were significantly down-regulated. Taken together, our data strongly indicated that HMGB1 might enhance p53 expression, which was associated with both the proliferative activity as well as apoptosis of T cells.

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