1. CD7 expression and galectin-1-induced apoptosis of immature thymocytes are directly regulated by NF-kappaB upon T-cell activation.
- Author
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Koh HS, Lee C, Lee KS, Ham CS, Seong RH, Kim SS, and Jeon SH
- Subjects
- Animals, Down-Regulation, Galectin 1 pharmacology, Lymphocyte Activation, Mice, Promoter Regions, Genetic drug effects, Repressor Proteins metabolism, Ribosomal Protein S6 Kinases, 90-kDa antagonists & inhibitors, Ribosomal Protein S6 Kinases, 90-kDa metabolism, Sp1 Transcription Factor metabolism, T-Lymphocytes drug effects, TCF Transcription Factors metabolism, Transcription Factor 7-Like 1 Protein, Twist-Related Protein 1 metabolism, p38 Mitogen-Activated Protein Kinases antagonists & inhibitors, p38 Mitogen-Activated Protein Kinases metabolism, Antigens, CD7 genetics, Apoptosis, Galectin 1 metabolism, Gene Expression Regulation, Developmental, NF-kappa B metabolism, T-Lymphocytes immunology
- Abstract
CD7, one of the galectin-1 receptors, has crucial roles in galectin-1-mediated apoptosis of activated T-cells and T-lymphoma progression in peripheral tissues. In this study, we showed that CD7 promoter activity was increased by NF-kappaB and that this activity was synergistic when Sp1 was co-expressed in the immature T-cell line L7. Site-directed mutagenesis analysis of the CD7 promoter indicated that NF-kappaB specifically bound to the NF-kappaE2 site in cooperation with Sp1. Overexpression of E12 or Twist2 proteins negatively regulated NF-kappaB-mediated activity of the CD7 proximal promoter. In addition, CD7 expression was down-regulated by treatment with the p38 MAPK inhibitor SB20358, or the MSK1 inhibitor H-89. These signaling pathway inhibitors prevented galectin-1-mediated apoptosis of immature T-cells. From these results, we concluded that the regulation of CD7 gene expression through NF-kappaB activation induced by TCR/CD28 might have significant implications for T-cell homeostasis.
- Published
- 2008
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