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사람 T 세포주에서 종양세포 배양액에 의한 TIM-3 발현 증가
- Alternative Title
- Su Jin Yun
- Author(s)
- 윤수진
- Alternative Author(s)
- Su Jin Yun
- Advisor
- 박선
- Department
- 일반대학원 의생명과학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2017-02
- Language
- eng
- Alternative Abstract
- T cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) is well known as one of the immune check point molecules. TIM-3 expressed on Th1 cells negatively regulates Th1 cell functions. TIM-3 expression is induced on exhausted T cells and senescent T cells in various diseases including autoimmune diseases, inflammatory diseases and cancers. However, the regulatory mechanism of TIM-3 expression in immune disorders has not been explored. Therefore, I wanted to investigate the regulatory mechanism of TIM-3 expression in a human T cell line cultured in the condition mimicking tumor microenvironment. TIM-3 mRNA and protein levels were promoted in Jurkat T cells cultured in tumor cell conditioned media (CM) or stimulated with agent elevating intracellular cyclic adenosine monophosphate (cAMP) concentration. Activation of protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac), molecules involved in cAMP downstream pathway, also increased TIM-3 expression in Jurkat T cells. Especially, inhibition of PKA pathway attenuated tumor CM-induced TIM-3 expression as well as cAMP-induced TIM-3 expression. Prostaglandin E2 (PGE2) which elevates intracellular cAMP levels, increased in tumor CM and slightly up-regulated TIM-3 expression in Jurkat T cells, however, tumor CM- induced TIM-3 expression was not affected by treatment with antagonist to PGE2 receptors. On the other hand, cAMP responsiveness of TIM-3 minimal promoter was shown. Collectively, this study demonstrates that TIM-3 expression is enhanced by incubation of Jurkat T cells in tumor CM or activation of cAMP/PKA/Epac pathway. These results provide insights to the regulation of TIM-3 expression in tumor and these insights could serve as the foundation for developing an approach for regulation of TIM-3 expression.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Biomedical Sciences > 4. Theses(Ph.D)
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