AUTHOR=Yoo Eun Jin , Lee Hwan Hee , Ye Byeong Jin , Lee Jun Ho , Lee Chae Young , Kang Hyun Je , Jeong Gyu Won , Park Hyun , Lim Sun Woo , Lee-Kwon Whaseon , Kwon Hyug Moo , Choi Soo Youn TITLE=TonEBP Suppresses the HO-1 Gene by Blocking Recruitment of Nrf2 to Its Promoter JOURNAL=Frontiers in Immunology VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.00850 DOI=10.3389/fimmu.2019.00850 ISSN=1664-3224 ABSTRACT=

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.