Activation of mitogen activated protein kinase-Erk kinase (MEK) increases T cell immunoglobulin mucin domain-3 (TIM-3) transcription in human T lymphocytes and a human mast cell line

作者：Yoon Soo Jin; Lee Mi Jin; Shin Dong Chul; Kim Jung Sik; Chwae Yong Joon; Kwon Myung Hee; Kim Kyongmin; Park Sun^*

来源：Molecular Immunology, 2011, 48(15-16): 1778-1783.

DOI：10.1016/j.molimm.2011.05.004

• TIM-3
• MEK
• Transcription
• T cell
• Mast cell

The immune regulatory molecule T cell immunoglobulin mucin domain (TIM-3) is expressed in activated T cells and in mast cells treated with transforming growth factor (TGF)-beta, but underlying mechanisms for induction of TIM-3 transcription have not been well-explored. We studied the role of mitogen-activated protein kinase (MAPK) in TIM-3 transcription on the basis of the involvement of MAPK in T cell activation and TGF-beta signaling. Inhibitors of MAPK-Erk kinase (MEK) as well as p38 suppressed TIM-3 transcription in phorbol myristic acid (PMA)-stimulated T cells, but inhibitors of c-Jun NH2-terminal kinase (JNK) did not. MEK over-expression enhanced TIM-3 transcription in PMA-stimulated T cells. Furthermore, 1.5 kb TIM-3 promoter was activated by PMA stimulation and repressed by MEK inhibitors in Jurkat T cells. Similarly, MEK activation enhanced TIM-3 transcription in TGF-beta-stimulated HMC-1 human mast cells, although MEK seemed not directly activated by TGF-beta. Concordantly, 1.5 kb TIM-3 promoter activity was reduced by MEK inhibitors, but was not responsive to TGF-beta stimulation in HMC-1 cells. These results suggest the regulatory role of MEK in TIM-3 transcription by human CD4+ T cells and mast cells.

• 出版日期2011-9