In order to investigate the effect of CD4 engagement on the transforming growth factor beta1 (TGF-beta1) promoter activity in haemopoietic progenitors, HEL cells were transiently transfected with a plasmid vector containing -453/+11 nucleotides of the TGF-beta1 promoter fused with the bacterial chloramphenicol acetyltransferase (CAT) gene and then treated with various agonists. Both cross-linked 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 CD8 mAb or p24. By using deletion mutants of the TGFbeta1 promoter, we found that the minimal DNA sequence still responsive to cross-linked CD4 mAb or gp120 was located between nucleotides -453/-323 of the TGF-beta1 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-beta1 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-beta1 expression, acting predominantly at the transcriptional level.

The engagement of CD4 surface antigen in the HEL haemopoietic cell line up-regulates the transforming growth factor-?1 (TGF-?1) promoter activity

D Gibellini;
1997

Abstract

In order to investigate the effect of CD4 engagement on the transforming growth factor beta1 (TGF-beta1) promoter activity in haemopoietic progenitors, HEL cells were transiently transfected with a plasmid vector containing -453/+11 nucleotides of the TGF-beta1 promoter fused with the bacterial chloramphenicol acetyltransferase (CAT) gene and then treated with various agonists. Both cross-linked 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 CD8 mAb or p24. By using deletion mutants of the TGFbeta1 promoter, we found that the minimal DNA sequence still responsive to cross-linked CD4 mAb or gp120 was located between nucleotides -453/-323 of the TGF-beta1 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-beta1 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-beta1 expression, acting predominantly at the transcriptional level.
TGF-beta1, CD4, HEL haemopoietic cell line
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/1079024
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 3
  • ???jsp.display-item.citation.isi??? ND
social impact