CD7 expression and galectin-1-induced apoptosis of immature thymocytes are directly regulated by NF-kappaB upon T-cell activation

Biochem Biophys Res Commun. 2008 May 23;370(1):149-53. doi: 10.1016/j.bbrc.2008.03.049. Epub 2008 Mar 18.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD7 / genetics*
  • Apoptosis*
  • Down-Regulation
  • Galectin 1 / metabolism*
  • Galectin 1 / pharmacology
  • Gene Expression Regulation, Developmental*
  • Lymphocyte Activation
  • Mice
  • NF-kappa B / metabolism*
  • 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
  • T-Lymphocytes / immunology*
  • 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

Substances

  • Antigens, CD7
  • Galectin 1
  • NF-kappa B
  • Repressor Proteins
  • Sp1 Transcription Factor
  • TCF Transcription Factors
  • Tcf7l1 protein, mouse
  • Transcription Factor 7-Like 1 Protein
  • Twist-Related Protein 1
  • Twist2 protein, mouse
  • Ribosomal Protein S6 Kinases, 90-kDa
  • mitogen and stress-activated protein kinase 1
  • p38 Mitogen-Activated Protein Kinases