Image_5_TonEBP Suppresses the HO-1 Gene by Blocking Recruitment of Nrf2 to Its Promoter.tiff (754.17 kB)

Image_5_TonEBP Suppresses the HO-1 Gene by Blocking Recruitment of Nrf2 to Its Promoter.tiff

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posted on 18.04.2019 by Eun Jin Yoo, Hwan Hee Lee, Byeong Jin Ye, Jun Ho Lee, Chae Young Lee, Hyun Je Kang, Gyu Won Jeong, Hyun Park, Sun Woo Lim, Whaseon Lee-Kwon, Hyug Moo Kwon, Soo Youn Choi

TonEBP is a key transcriptional activator in macrophages with an M1 phenotype. High expression of TonEBP is associated with many inflammatory diseases. Heme oxygenase-1 (HO-1), a stress-inducible protein, is induced by various oxidative and inflammatory signals, and its expression is regarded as an adaptive cellular response to inflammation and oxidative injury. Here, we show that TonEBP suppresses expression of HO-1 by blocking Nrf2 binding to the HO-1 promoter, thereby inducing polarization of macrophages to the M1 phenotype. Inhibition of HO-1 expression or activity significantly reduced the inhibitory responses on M1 phenotype and stimulatory effects on M2 phenotype by TonEBP knockdown. Additional experiments showed that HO-1 plays a role in the paracrine anti-inflammatory effects of TonEBP knockdown in macrophages. Identification of HO-1 as a downstream effector of TonEBP provides new possibilities for improved therapeutic approaches to inflammatory diseases.

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