Requirement for cooperative interaction of interleukin-6 responsive element type 2 and glucocorticoid responsive element in the synergistic activation of mouse metallothionein-I gene by interleukin-6 and glucocorticoid.
Toxicol Appl Pharmacol
; 151(1): 143-51, 1998 Jul.
Article
em En
| MEDLINE
| ID: mdl-9705897
ABSTRACT
Metallothionein (MT)-inducing activity of interleukin (IL)-6 depends on the presence of glucocorticoid in hepatic cells. The synergistic action of IL-6 and glucocorticoid was observed in the transcriptional activation of the mouse MT (mMT)-I gene. We found that a 281-bp promoter was sufficient for IL-6 and glucocorticoid stimulation. Our inspection of this region revealed the putative type 1 and 2 IL-6 responsive elements (REs). Functional analyses of these regions were performed using luciferase reporter constructs, and it was observed that the type 2 IL-6RE exerted the major response to the IL-6 signal. The transcriptional factor binding to type 1 IL-6RE, nuclear factor-IL-6, hardly contributed to the activation of the mMT-I promoter by IL-6 and glucocorticoid. A glucocorticoid responsive element (GRE) was also required for the synergistic activation by IL-6 and glucocorticoid. Interestingly, this synergism was not observed when the type 2 IL-6RE and the GRE were kept apart. Therefore, the synergistic activation of the mMT-I gene by IL-6 and glucocorticoid may require not only that signal transducers and activators 3 (Stat3) and the glucocorticoid receptor (GR) bind to their respective responsive elements, but also that Stat3 and the GR physically interact with one another.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Interleucina-6
/
Proteínas de Ligação a DNA
/
Glucocorticoides
/
Metalotioneína
Limite:
Animals
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Japão