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 | |
| State | Published - May 1 2013 |
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ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
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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, 01.05.2013, p. 461-469.Research output: Contribution to journal › Article
TY - JOUR
T1 - Suppression of inflammation and acute lung injury by Miz1 via repression of C/EBP-δ
AU - Do-Umehara, Hanh Chi
AU - Chen, Cong
AU - Urich, Daniela
AU - Zhou, Liang
AU - Qiu, Ju
AU - Jang, Samuel
AU - Zander, Alia
AU - Baker, Margaret A.
AU - Eilers, Martin
AU - Sporn, Peter H S
AU - Ridge, Karen M.
AU - Sznajder, Jacob I.
AU - Budinger, G. R Scott
AU - Mutlu, Gökhan M.
AU - Lin, Anning
AU - Liu, Jing
PY - 2013/5/1
Y1 - 2013/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84876672758&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84876672758&partnerID=8YFLogxK
U2 - 10.1038/ni.2566
DO - 10.1038/ni.2566
M3 - Article
C2 - 23525087
AN - SCOPUS:84876672758
VL - 14
SP - 461
EP - 469
JO - Nature Immunology
JF - Nature Immunology
SN - 1529-2908
IS - 5
ER -