| First Author | Wruck CJ | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 6 | Pages | 4493-9 |
| PubMed ID | 21127061 | Mgi Jnum | J:169489 |
| Mgi Id | MGI:4941104 | Doi | 10.1074/jbc.M110.162008 |
| Citation | Wruck CJ, et al. (2011) Nrf2 induces interleukin-6 (IL-6) expression via an antioxidant response element within the IL-6 promoter. J Biol Chem 286(6):4493-9 |
| abstractText | IL-6 gene expression is controlled by a promoter region containing multiple regulatory elements such as NF-kappaB, NF-IL6, CRE, GRE, and TRE. In this study, we demonstrated that TRE, found within the IL-6 promoter, is embedded in a functional antioxidant response element (ARE) matching an entire ARE consensus sequence. Further, point mutations of the ARE consensus sequence in the IL-6 promoter construct selectively eliminate ARE but not TRE activity. Nrf2 is a redox-sensitive transcription factor which provides cytoprotection against electrophilic and oxidative stress and is the most potent activator of ARE-dependent transcription. Using Nrf2 knock-out mice we demonstrate that Nrf2 is a potent activator of IL-6 gene transcription in vivo. Moreover, we show evidence that Nrf2 is the transcription factor that activates IL6 expression in a cholestatic hepatitis mouse model. Our findings suggest a possible role of IL-6 in oxidative stress defense and also give indication about an important function for Nrf2 in the regulation of hematopoietic and inflammatory processes. |
