期刊
MOLECULAR AND CELLULAR BIOCHEMISTRY
卷 434, 期 1-2, 页码 75-87出版社
SPRINGER
DOI: 10.1007/s11010-017-3038-5
关键词
Staphylococcal enterotoxin A; Cancer immunotherapy; MEK/ERK pathway; STATs; PBMCs; Cytokines
类别
资金
- National Natural Science Foundation of China [81301948]
- Grow Seedlings Project of Department of Education of Guangdong Province [2013LYM0070]
- Natural Science Foundation from Guangdong Science and Technology Department [2014A020212343]
Staphylococcal enterotoxin A (SEA) is well known as a superantigen and is highly potent in activating T lymphocytes. And it has been used clinically as an immunomodifier in the treatment of a number of tumors for years. However, the mechanism of its action remains largely unclear. In this study, SEA was found to significantly inhibit the proliferation and induce the death of human lung carcinoma A549 cells when co-cultured with human peripheral blood mononuclear cells (PBMCs). SEA could also induce the proliferation of human PBMCs and stimulate human PBMCs to release a wide range of cytokines that have broad anti-tumor activities such as IFN-gamma, TNF-alpha, IL-2. Furthermore, SEA was found in PBMCs to induce a rapid and long-lasting phosphorylation of extracellular signal-regulated kinases (ERKs) which was significantly inhibited by MEK/ERK pathway inhibitors U0126 and PD0325901, and a late onset of phosphorylation of signal transducers and activators of transcription (STATs) which was significantly inhibited by a pan-JAK inhibitor Pyridone 6 (P6). Unexpectedly constitutive ERK or STATs phosphorylation was also significantly inhibited by P6 or U0126 in a dose-dependent manner, respectively. Summing up, our data reveal SEA may function as a novel protein drug used for cancer immunotherapy via inducing activation of PBMCs, immune cell crosstalk-dependent activation of ERK and STATs, and production of tumor-suppressive cytokines.
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