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
| Autor: | Norio Itoh, Masako Kanekiyo, Norio Muto, Keiichi Tanaka, Keiko Kasutani |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
STAT3 Transcription Factor
medicine.medical_specialty Molecular Sequence Data Biology Toxicology Mice Glucocorticoid receptor Internal medicine medicine Tumor Cells Cultured Metallothionein Animals STAT3 Interleukin 6 Promoter Regions Genetic Gene Glucocorticoids Pharmacology Interleukin-6 Interleukin Drug Synergism Cell biology Rats DNA-Binding Proteins Endocrinology Gene Expression Regulation biology.protein Hepatic stellate cell Trans-Activators Glucocorticoid medicine.drug Acute-Phase Proteins Transcription Factors |
| Zdroj: | Toxicology and applied pharmacology. 151(1) |
| ISSN: | 0041-008X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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