title: 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.
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.
authors.affiliation: Department of Microbiology, Ajou University School of Medicine, Youngtongku Wonchondong San 5, Suwon 442-749, Republic of Korea.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Yoon
authors.forename: Mi Jin
authors.initials: MJ
authors.lastname: Lee
authors.forename: Dong-Chul
authors.initials: DC
authors.lastname: Shin
authors.forename: Jung Sik
authors.initials: JS
authors.lastname: Kim
authors.forename: Yong-Joon
authors.initials: YJ
authors.lastname: Chwae
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Kwon
authors.forename: Kyongmin
authors.initials: K
authors.lastname: Kim
authors.forename: Sun
authors.initials: S
authors.lastname: Park
mesh_terms: D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation / Q000276:immunology; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000276:immunology*; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D048369:MAP Kinase Kinase 1 / Q000276:immunology / Q000378:metabolism*; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; D048369:MAP Kinase Kinase 1