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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

Authors
Yoon, SJ; Lee, MJ; Shin, DC; Kim, JS; Chwae, YJ; Kwon, MH; Kim, K; Park, S
Citation
Molecular immunology, 48(15-16):1778-1783, 2011
Journal Title
Molecular immunology
ISSN
0161-58901872-9142
Abstract
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)-β, 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-β 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, -1.5kb 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-β-stimulated HMC-1 human mast cells, although MEK seemed not directly activated by TGF-β. Concordantly, -1.5kb TIM-3 promoter activity was reduced by MEK inhibitors, but was not responsive to TGF-β 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.
MeSH terms
Blotting, WesternCD4-Positive T-Lymphocytes/immunology/*metabolismCell LineEnzyme Activation/immunologyGene ExpressionGene Expression Regulation/*immunologyHumansLymphocyte Activation/immunologyMAP Kinase Kinase 1/immunology/*metabolismMast Cells/immunology/*metabolismMembrane Proteins/genetics/immunology/*metabolismReverse Transcriptase Polymerase Chain Reaction*Transcription, Genetic
DOI
10.1016/j.molimm.2011.05.004
PMID
21621846
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
AJOU Authors
이, 미진최, 용준권, 명희김, 경민박, 선
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