Nrf2 Induces Interleukin-6 (IL-6) Expression via an Antioxidant Response Element within the IL-6 Promoter

作者：Wruck Christoph Jan^*; Streetz Konrad; Pavic Goran; Goetz Mario E; Tohidnezhad Mersedeh; Brandenburg Lars Ove; Varoga Deike; Eickelberg Oliver; Herdegen Thomas; Trautwein Christian; Cha Kaimin; Kan Yuet Wai; Pufe Thomas

来源：Journal of Biological Chemistry, 2011, 286(6): 4493-4499.

DOI：10.1074/jbc.M110.162008

IL-6 gene expression is controlled by a promoter region containing multiple regulatory elements such as NF-kappa B, 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.

• 出版日期2011-2