| Autor: |
Grall, Franck T., Prall, Wolf C., Wei, Wanjiang, Gu, Xuesong, Cho, Je-Yoel, Choy, Bob K., Zerbini, Luiz F., Inan, Mehmet S., Goldring, Steven R., Gravallese, Ellen M., Goldring, Mary B., Oettgen, Peter, Libermann, Towia A. |
| Předmět: |
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| Zdroj: |
FEBS Journal; Apr2005, Vol. 272 Issue 7, p1676-1687, 12p |
| Abstrakt: |
Cyclooxygenase-2 (COX-2) is a key enzyme in the production of prostaglandins that are major inflammatory agents. COX-2 production is triggered by exposure to various cytokines and to bacterial endotoxins. We present here a novel role for the Ets transcription factor ESE-1 in regulating theCOX-2gene in response to endotoxin and other pro-inflammatory stimuli. We report that the induction ofCOX-2expression by lipopolysaccharide (LPS) and pro-inflammatory cytokines correlates with ESE-1 induction in monocyte/macrophages. ESE-1, in turn, binds to several E26 transformation specific (Ets) sites on theCOX-2promoter.In vitroanalysis demonstrates that ESE-1 binds to and activates theCOX-2promoter to levels comparable to LPS-mediated induction. Moreover, we provide results showing that the induction ofCOX-2by LPS may require ESE-1, as the mutation of the Ets sites in theCOX-2promoter or overexpression of a dominant-negative form of ESE-1 inhibits LPS-mediated COX-2 induction. The effect of ESE-1 on theCOX-2promoter is further enhanced by cooperation with other transcription factors such as nuclear factor-κB and nuclear factor of activated T cells. Neutralization of COX-2 is the goal of many anti-inflammatory drugs. As an activator of COX-2 induction, ESE-1 may become a target for such therapeutics as well. Together with our previous reports of the role of ESE-1 as an inducer of nitric oxide synthase in endothelial cells and as a mediator of pro-inflammatory cytokines in vascular and connective tissue cells, these results establish ESE-1 as an important player in the regulation of inflammation. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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