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-kappa B and that this activity was synergistic when Sol was co-expressed in the immature T-cell line L7. Site-directed mutagenesis analysis of the CD7 promoter indicated that NF-kappa B specifically bound to the NF-kappa E2 site in cooperation with Sp1. Overexpression of E12 or Twist2 proteins negatively regulated NF-kappa B-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-kappa B activation induced by TCR/CD28 might have significant implications for T-cell homeostasis. (c) 2008 Elsevier Inc. All rights reserved.