期刊
TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 251, 期 2, 页码 130-136出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2010.12.011
关键词
Erlotinib; T cells; Immunosuppression; c-Raf/ERK; Akt
资金
- National Natural Science Foundation of China (NSFC) [30730107, 90913023]
- Science Fund for Creative Research Groups of NSFC [30821006]
- Provincial Science Foundation of Jiangsu [BK2008022, BK2010579]
- National Science and Technology Major Project [2009ZX09102-129, 2009ZX09303-001]
Erlotinib is a potent inhibitor of epidermal growth factor receptor tyrosine kinase and has been demonstrated to treat advanced or metastatic non-small cell lung cancer to prolong survival after failure of first-line or second-line chemotherapy. However, little is known about its effects on immune system. In the present study, we aimed to investigate the immunosuppressive activity of erlotinib on T lymphocytes both in vitro and in vivo, and further explore its potential molecular mechanism. Erlotinib exerted a significant inhibition on the T cell proliferation and activation induced by concanavalin A, anti-CD3 plus anti-CD28, staphylococcal enterotoxin B or phorbol myristate acetate respectively in a concentration-dependent manner and it also inhibited the secretion of the proinflammatory cytokines such as IL-2 and IFN-gamma of activated T cells. Further study showed that erlotinib caused G0/G1 arrest and suppressed the phosphorylations of c-Raf, ERK and Akt in activated T cells. Moreover, erlotinib significantly ameliorated picryl chloride-induced ear contact dermatitis in a dose-dependent manner in vivo. In summary, these findings suggest that erlotinib may cause the impairment of T-cell-mediated immune response both in vitro and in vivo through inhibiting T cell proliferation and activation, which is closely associated with its potent down-regulation of the c-Raf/ERK cascade and Akt signaling pathway. (C) 2010 Elsevier Inc. All rights reserved.
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