Thioredoxin-2 impacts the inflammatory response via suppression of NF-κB and MAPK signaling in sepsis shock

Xi Wang; Yanyan Xing; Zhongyan Tang; Yuedong Tang; Jie Shen; Feng Zhang

doi:10.1016/j.bbrc.2020.01.169

Thioredoxin-2 impacts the inflammatory response via suppression of NF-κB and MAPK signaling in sepsis shock

Biochem Biophys Res Commun. 2020 Apr 16;524(4):876-882. doi: 10.1016/j.bbrc.2020.01.169. Epub 2020 Feb 11.

Authors

Xi Wang¹, Yanyan Xing², Zhongyan Tang¹, Yuedong Tang¹, Jie Shen³, Feng Zhang⁴

Affiliations

¹ Department of Emergency and Critical Care Medicine, Jinshan Hospital, Fudan University, Shanghai, 201508, China.
² Department of Obstetrics and Gynecology, Jinshan Hospital, Fudan University, Shanghai, 201508, China.
³ Department of Emergency and Critical Care Medicine, Jinshan Hospital, Fudan University, Shanghai, 201508, China. Electronic address: [email protected].
⁴ Department of Emergency and Critical Care Medicine, Jinshan Hospital, Fudan University, Shanghai, 201508, China. Electronic address: [email protected].

PMID: 32057359
DOI: 10.1016/j.bbrc.2020.01.169

Abstract

Sepsis is a progressive disease characterized by excessive inflammatory responses, severe tissue injury and organ dysfunction, ultimately leading to mortality. In this study, we demonstrated that thioredoxin-2 (TRX-2) expression is reduced in macrophages stimulated with lipopolysaccharide (LPS). Overexpression of TRX-2 significantly attenuated interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) production induced by LPS. TRX-2 inhibited LPS-induced inflammatory responses through suppressing activation of the NF-κB and MAPK signaling pathways. Furthermore, TRX-2 induced a significant decrease in mortality in mouse sepsis models in association with reduced inflammatory cytokine production and attenuation of organ injury. Our data collectively support a role of TRX-2 as a critical regulator of sepsis that influences survival by protecting the host from excessive inflammatory damage.

Keywords: Inflammatory; MAPK; NF-κB; Sepsis; TRX-2.

MeSH terms

Animals
Gene Expression Regulation
Interleukin-6 / genetics
Interleukin-6 / metabolism
Lipopolysaccharides / administration & dosage
Liver / drug effects
Liver / metabolism
Liver / pathology
Macrophages, Peritoneal / drug effects
Macrophages, Peritoneal / metabolism*
Macrophages, Peritoneal / pathology
Male
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinases / genetics*
Mitogen-Activated Protein Kinases / metabolism
NF-kappa B / genetics*
NF-kappa B / metabolism
RAW 264.7 Cells
Shock, Septic / chemically induced
Shock, Septic / genetics*
Shock, Septic / mortality
Shock, Septic / pathology
Signal Transduction
Survival Analysis
Thioglycolates / pharmacology
Thioredoxins / genetics*
Thioredoxins / metabolism
Tumor Necrosis Factor-alpha / genetics
Tumor Necrosis Factor-alpha / metabolism

Substances

Interleukin-6
Lipopolysaccharides
NF-kappa B
Thioglycolates
Tumor Necrosis Factor-alpha
Txn2 protein, mouse
interleukin-6, mouse
Thioredoxins
2-mercaptoacetate
Mitogen-Activated Protein Kinases