HSF1 Protects Sepsis-Induced Acute Lung Injury by Inhibiting NLRP3 Inflammasome Activation

Xueyan Shi; Xueyan Shi; Tao Li; Tao Li; Yanting Liu; Yanting Liu; Leijin Yin; Leijin Yin; Lan Xiao; Liyao Fu; Liyao Fu; Yaxi Zhu; Yaxi Zhu; Huan Chen; Huan Chen; Kangkai Wang; Kangkai Wang; Xianzhong Xiao; Xianzhong Xiao; Huali Zhang; Huali Zhang; Sichuang Tan; Sipin Tan; Sipin Tan

doi:10.3389/fimmu.2022.781003

Frontiers in Immunology (Jun 2022)

HSF1 Protects Sepsis-Induced Acute Lung Injury by Inhibiting NLRP3 Inflammasome Activation

Xueyan Shi,
Xueyan Shi,
Tao Li,
Tao Li,
Yanting Liu,
Yanting Liu,
Leijin Yin,
Leijin Yin,
Lan Xiao,
Liyao Fu,
Liyao Fu,
Yaxi Zhu,
Yaxi Zhu,
Huan Chen,
Huan Chen,
Kangkai Wang,
Kangkai Wang,
Xianzhong Xiao,
Xianzhong Xiao,
Huali Zhang,
Huali Zhang,
Sichuang Tan,
Sipin Tan,
Sipin Tan

Affiliations

Xueyan Shi: Sepsis Translational Medicine Key Laboratory of Hunan Province, Central South University, Changsha, China
Xueyan Shi: State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research, Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union, Medical College, Beijing, China
Tao Li: Sepsis Translational Medicine Key Laboratory of Hunan Province, Central South University, Changsha, China
Tao Li: Department of Pathophysiology, Medical College of Jiaying University, Meizhou, China
Yanting Liu: Sepsis Translational Medicine Key Laboratory of Hunan Province, Central South University, Changsha, China
Yanting Liu: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, China
Leijin Yin: Sepsis Translational Medicine Key Laboratory of Hunan Province, Central South University, Changsha, China
Leijin Yin: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, China
Lan Xiao: Department of Traditional Chinese Medicine, The Third Xiangya Hospital, Central South University, Changsha, China
Liyao Fu: Sepsis Translational Medicine Key Laboratory of Hunan Province, Central South University, Changsha, China
Liyao Fu: The Second Xiangya Hospital, Central South University, Changsha, China
Yaxi Zhu: Sepsis Translational Medicine Key Laboratory of Hunan Province, Central South University, Changsha, China
Yaxi Zhu: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, China
Huan Chen: Sepsis Translational Medicine Key Laboratory of Hunan Province, Central South University, Changsha, China
Huan Chen: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, China
Kangkai Wang: Sepsis Translational Medicine Key Laboratory of Hunan Province, Central South University, Changsha, China
Kangkai Wang: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, China
Xianzhong Xiao: Sepsis Translational Medicine Key Laboratory of Hunan Province, Central South University, Changsha, China
Xianzhong Xiao: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, China
Huali Zhang: Sepsis Translational Medicine Key Laboratory of Hunan Province, Central South University, Changsha, China
Huali Zhang: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, China
Sichuang Tan: The Second Xiangya Hospital, Central South University, Changsha, China
Sipin Tan: Sepsis Translational Medicine Key Laboratory of Hunan Province, Central South University, Changsha, China
Sipin Tan: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, China

DOI: https://doi.org/10.3389/fimmu.2022.781003
Journal volume & issue: Vol. 13

Abstract

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As an important transcription factor, heat shock factor 1 (HSF1) plays an endogenous anti-inflammation role in the body and can alleviate multiple organ dysfunction caused by sepsis, which contributes to an uncontrolled inflammatory response. The NLRP3 inflammasome is a supramolecular complex that plays key roles in immune surveillance. Inflammation is accomplished by NLRP3 inflammasome activation, which leads to the proteolytic maturation of IL-1β and pyroptosis. However, whether HSF1 is involved in the activation of the NLRP3 inflammasome in septic acute lung injury (ALI) has not been reported. Here, we show that HSF1 suppresses NLRP3 inflammasome activation in transcriptional and post-translational modification levels. HSF1 can repress NLRP3 expression via inhibiting NF-κB phosphorylation. HSF1 can inhibit caspase-1 activation and IL-1β maturation via promoting NLRP3 ubiquitination. Our finding not only elucidates a novel mechanism for HSF1-mediated protection of septic ALI but also identifies new therapeutic targets for septic ALI and related diseases.

Published in Frontiers in Immunology

ISSN: 1664-3224 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy
Website: http://journal.frontiersin.org/journal/immunology

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