Suppression of inflammation and acute lung injury by Miz1 via repression of C/EBP-δ

Hanh Chi Do-Umehara, Cong Chen, Daniela Urich, Liang Zhou, Ju Qiu, Samuel Jang, Alia Zander, Margaret A. Baker, Martin Eilers, Peter H S Sporn, Karen M. Ridge, Jacob I. Sznajder, G. R Scott Budinger, Gökhan M. Mutlu, Anning Lin, Jing Liu*

*Corresponding author for this work

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Inflammation is essential for host defense but can cause tissue damage and organ failure if unchecked. How the inflammation is resolved remains elusive. Here we report that the transcription factor Miz1 was required for terminating lipopolysaccharide (LPS)-induced inflammation. Genetic disruption of the Miz1 POZ domain, which is essential for the transactivation or repression activity of Miz1, resulted in hyperinflammation, lung injury and greater mortality in LPS-treated mice but a lower bacterial load and mortality in mice with Pseudomonas aeruginosa pneumonia. Loss of the Miz1 POZ domain prolonged the expression of proinflammatory cytokines. After stimulation, Miz1 was phosphorylated at Ser178, which was required for recruitment of the histone deacetylase HDAC1 to repress transcription of the gene encoding C/EBP-δ, an amplifier of inflammation. Our data provide a long-sought mechanism underlying the resolution of LPS-induced inflammation.

Original languageEnglish (US)
Pages (from-to)461-469
Number of pages9
JournalNature Immunology
Volume14
Issue number5
DOIs
StatePublished - May 1 2013

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Do-Umehara, H. C., Chen, C., Urich, D., Zhou, L., Qiu, J., Jang, S., Zander, A., Baker, M. A., Eilers, M., Sporn, P. H. S., Ridge, K. M., Sznajder, J. I., Budinger, G. R. S., Mutlu, G. M., Lin, A., & Liu, J. (2013). Suppression of inflammation and acute lung injury by Miz1 via repression of C/EBP-δ. Nature Immunology, 14(5), 461-469. https://doi.org/10.1038/ni.2566