12-O-tetradecanoylphorbol-13-acetate- and tumor necrosis factor alpha-mediated induction of intercellular adhesion molecule-1 is inhibited by dexamethasone. Functional analysis of the human intercellular adhesion molecular-1 promoter.
Transcription regulation of the human intercellular adhesion molecule-1 gene by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), tumor necrosis factor alpha (TNF alpha), and the glucocorticoid dexamethasone was studied using transient transfections in 293 cells with intercellular adhesion molecule-1 promoter-luciferase constructs (together with a glucocorticoid receptor expression vector). TPA and TNF alpha induced promoter activity, which was repressed by dexamethasone. Four TPA-responsive DNA regions were identified, each containing a potential TPA-responsive enhancer sequence: 1) -677/-340 an AP3-like sequence; 2) -290/278 a TPA-response element (TRE); 3) -227/-175 an NF kappa B-like sequence; 4) -105/-38 an AP2-like sequence. TNF alpha enhanced transcription only through region 3. The TRE in region 2 appeared to be functionally coupled to a distal TATA box at -313 and differed from the consensus TRE with respect to binding characteristics for members of the AP1 family. The newly identified NF kappa B enhancer (TGGAAATTCC) is bound by a TNF alpha-induced nuclear protein and appears to be the key element in rapid transcription induction by TNF alpha (and TPA), while transactivation of this element is repressed by the ligand-bound glucocorticoid receptor. We propose a negative cross-talk between the NF kappa B transcription factor and the glucocorticoid receptor.
van de Stolpe
A
A
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht.
Caldenhoven
E
E
Stade
B G
BG
Koenderman
L
L
Raaijmakers
J A
JA
Johnson
J P
JP
van der Saag
P T
PT
D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D017931:DNA Primers; D003907:Dexamethasone / Q000494:pharmacology*; D004742:Enhancer Elements, Genetic; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D015815:Cell Adhesion Molecules; D017931:DNA Primers; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D003907:Dexamethasone; D013755:Tetradecanoylphorbol Acetate