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

doi:10.1038/ni.2566

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

Medicine, Pulmonary Division

Research output: Contribution to journal › Article › peer-review

61 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 language	English (US)
Pages (from-to)	461-469
Number of pages	9
Journal	Nature Immunology
Volume	14
Issue number	5
DOIs	https://doi.org/10.1038/ni.2566
State	Published - May 2013

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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Do-Umehara, Hanh Chi ; Chen, Cong ; Urich, Daniela ; Zhou, Liang ; Qiu, Ju ; Jang, Samuel ; Zander, Alia ; Baker, Margaret A. ; Eilers, Martin ; Sporn, Peter H S ; Ridge, Karen M. ; Sznajder, Jacob I. ; Budinger, G. R Scott ; Mutlu, Gökhan M. ; Lin, Anning ; Liu, Jing. / Suppression of inflammation and acute lung injury by Miz1 via repression of C/EBP-δ. In: Nature Immunology. 2013 ; Vol. 14, No. 5. pp. 461-469.

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

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.",

author = "Do-Umehara, {Hanh Chi} and Cong Chen and Daniela Urich and Liang Zhou and Ju Qiu and Samuel Jang and Alia Zander and Baker, {Margaret A.} and Martin Eilers and Sporn, {Peter H S} and Ridge, {Karen M.} and Sznajder, {Jacob I.} and Budinger, {G. R Scott} and Mutlu, {G{\"o}khan M.} and Anning Lin and Jing Liu",

note = "Funding Information: We thank A. Hauser, K. Gates, A. Gonzalez and F. Aguilar for help with animal experiments; J. Radder for isolating ATII cells; L. He for isolating lung cells derived from the hematopoietic compartment; A. Yemelyanov for lentivirus preparation; and J. Dewille (Ohio State University College of Veterinary Medicine) for the Cebpd luciferase reporter gene construct. Supported by the US National Institutes of Health (GM081603 to J.L., GM095313 to A.L., ES015024 to G.M.M., ES013995 to G.R.S.B., P01HL071643 to J.I.S., and AI 089954 and AI 091962 to L.Z.).",

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Suppression of inflammation and acute lung injury by Miz1 via repression of C/EBP-δ. / Do-Umehara, Hanh Chi; Chen, Cong; Urich, Daniela; Zhou, Liang; Qiu, Ju; Jang, Samuel; Zander, Alia; Baker, Margaret A.; Eilers, Martin; Sporn, Peter H S ; Ridge, Karen M.; Sznajder, Jacob I.; Budinger, G. R Scott; Mutlu, Gökhan M.; Lin, Anning; Liu, Jing.

In: Nature Immunology, Vol. 14, No. 5, 05.2013, p. 461-469.

Research output: Contribution to journal › Article › peer-review

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AU - Jang, Samuel

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AU - Budinger, G. R Scott

AU - Mutlu, Gökhan M.

AU - Lin, Anning

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

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