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.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Yoo EJ,Lee HH,Ye BJ,Lee JH,Lee CY,Kang HJ,Jeong GW,Park H,Lim SW,Lee-Kwon W,Kwon HM,Choi SYdoi
10.3389/fimmu.2019.00850subject
Has Abstractpub_date
2019-04-18 00:00:00pages
850issn
1664-3224journal_volume
10pub_type
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