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Updated: Jul 15, 2026
06:40
Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice
Published on: February 9, 2014
ATF4-histone 2-hydroxyisobutyrylation feedback loop drives sepsis-induced inflammation.
Liang Zhang1,2, Yongling Lu3, Hongmei Qiu1,2
1Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China.
British Journal of Pharmacology
|July 13, 2026
Summary
Lysine 2-hydroxyisobutyrylation (Khib) epigenetically regulates sepsis inflammation. The EP300/ATF4/H4K5-hib feedback loop promotes inflammation and is a potential therapeutic target for sepsis.
Area of Science:
- Epigenetics
- Molecular Biology
- Immunology
Background:
- Sepsis involves complex inflammatory responses.
- The precise epigenetic mechanisms driving acute sepsis inflammation are not fully understood.
- Lysine 2-hydroxyisobutyrylation (Khib) is a post-translational modification with unclear roles in sepsis.
Purpose of the Study:
- To investigate the role and mechanisms of histone H4 lysine 5 2-hydroxyisobutyrylation (H4K5-hib) in sepsis-induced inflammation.
- To elucidate the function of H4K5-hib in vivo and in vitro models of sepsis.
Main Methods:
- Sepsis model: caecal ligation and puncture (CLP) in mice.
- In vitro model: lipopolysaccharide (LPS)-stimulated macrophages.
- Techniques: CUT&Tag-seq, immunofluorescence, Western blotting, qPCR, dual-luciferase assays, ELISA.
Main Results:
- H4K5-hib levels increased during acute sepsis inflammation.
- H4K5-hib promotes ATF4 transcription via EP300, activating the ATF4/NLRP3 inflammasome axis.
- A positive feedback loop involving EP300, ATF4, and H4K5-hib amplifies inflammatory responses.
- Inhibition of EP300 or ATF4 reduced H4K5-hib and NLRP3 inflammasome activation in vivo.
Conclusions:
- A novel epigenetic mechanism involving the EP300/ATF4/H4K5-hib feedback loop drives sepsis-induced inflammation.
- This epigenetic loop represents a potential therapeutic target for managing sepsis.
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