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
Identifieur interne : 000C56 ( Main/Exploration ); précédent : 000C55; suivant : 000C57Requirement 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
Auteurs : Keiko Kasutani [Japon] ; Norio Itoh [Japon] ; Masako Kanekiyo [Japon] ; Norio Muto [Japon] ; Keiichi Tanaka [Japon]Source :
- Toxicology and Applied Pharmacology [ 0041-008X ] ; 1998.
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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DOI: 10.1006/taap.1998.8452
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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.</div></front></TEI><affiliations><list><country><li>Japon</li></country></list><tree><country name="Japon"><noRegion><name sortKey="Kasutani, Keiko" sort="Kasutani, Keiko" uniqKey="Kasutani K" first="Keiko" last="Kasutani">Keiko Kasutani</name></noRegion><name sortKey="Itoh, Norio" sort="Itoh, Norio" uniqKey="Itoh N" first="Norio" last="Itoh">Norio Itoh</name><name sortKey="Kanekiyo, Masako" sort="Kanekiyo, Masako" uniqKey="Kanekiyo M" first="Masako" last="Kanekiyo">Masako Kanekiyo</name><name sortKey="Muto, Norio" sort="Muto, Norio" uniqKey="Muto N" first="Norio" last="Muto">Norio Muto</name><name sortKey="Tanaka, Keiichi" sort="Tanaka, Keiichi" uniqKey="Tanaka K" first="Keiichi" last="Tanaka">Keiichi Tanaka</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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