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.
Mol Immunol
; 48(15-16): 1778-83, 2011 Sep.
Article
in En
| MEDLINE
| ID: mdl-21621846
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)-ß, 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-ß 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-ß-stimulated HMC-1 human mast cells, although MEK seemed not directly activated by TGF-ß. Concordantly, -1.5kb TIM-3 promoter activity was reduced by MEK inhibitors, but was not responsive to TGF-ß 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription, Genetic
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CD4-Positive T-Lymphocytes
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Gene Expression Regulation
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MAP Kinase Kinase 1
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Mast Cells
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Membrane Proteins
Limits:
Humans
Language:
En
Journal:
Mol Immunol
Year:
2011
Document type:
Article
Publication country:
ENGLAND
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ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
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REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM