In order to investigate the effect of CD4 engagement on the transforming growth factor beta 1 (TGF-beta 1) promoter activity in haemopoietic progenitors, HEL cells were transiently transfected with a plasmid vector containing -453/+ 11 nucleotides of the TGF-beta 1 promoter fused with the bacterial chloramphenicol acetyltransferase (CAT) gene and then treated with various agonists. Both crosslinked CD4mAb and envelope gp120 were able to significantly up-regulate CAT activity with respect to the levels of activation observed in HEL cells treated with cross-linked CD8mAb or p24. By using deletion mutants of the TGF beta 1 promoter, we found that the minimal DNA sequence still responsive to cross-linked CD4mAb or gp120 was located between nucleotides -453/- 323 of the TGF-beta 1 promoter, which contains two activating protein 1 (AP1) binding sites. In electromobility shift assays (EMSA) we could demonstrate that CD4 engagement of HEL cells induced a significant increase of AP1 binding activity at the nuclear level. Furthermore, the steady-state mRNA of endogenous TGF-beta 1 showed a small but reproducible increase when HEL cells were treated with cross-linked CD4mAb or gp120. Altogether, these findings suggest that the engagement of CD4 in HEL cells modulates TGF-beta 1 expression, acting predominantly at the transcriptional level.
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|Titolo:||The engagement of CD4 surface antigen in the HEL haemopoietic cell line up-regulates the transforming growth factor-beta1 (TGF-beta1) promoter activity|
|Data di pubblicazione:||1997|
|Appare nelle tipologie:||03.1 Articolo su rivista|