Intracellular and Extracellular Lipopolysaccharide Signaling in Sepsis: Avenues for Novel Therapeutic Strategies

Gabarin, Ramy S; Li, Manshu; Zimmel, Paige A; Marshall, John C.; Li, Yimin; Zhang, Haibo

doi:10.1159/000515740

Cited by 90 publications

(73 citation statements)

References 79 publications

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“…LPS is the main component of the cell wall of Gram-negative bacteria. Endotoxemia and systemic inflammatory response syndrome caused by Gram-negative bacteria infection are the main causes of acute lung injury in sepsis in children ( 24 ). Currently, LPS-induced lung injury of sepsis models are very mature, and the authenticity and reliability of LPS-induced septic lung injury have been confirmed ( 25 , 26 ).…”

Section: Discussionmentioning

confidence: 99%

Puerarin Inhibits Ferroptosis and Inflammation of Lung Injury Caused by Sepsis in LPS Induced Lung Epithelial Cells

Wang

Chen

2021

Front. Pediatr.

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Background: Ferroptosis is a new type of programmed cell death, which plays an important role in lung injury caused by sepsis. Studies have reported that Puerarin (Pue) can treat lung injury caused by sepsis in children, but whether it plays a role by regulating iron death has not been reported.Methods: LPS induced human alveolar epithelial cell A549 to form a model of lung injury caused by sepsis. MTT detected the effect of Pue on A549 cell viability and the effect of Pue on LPS-induced A549 cell viability. The effects of Pue on LPS-induced inflammatory cytokines TNF-α, IL-8, IL-1β in A549 cells were determined by ELISA assay. The expression level of MDA was detected by TBARS colorimetric quantitative detection kit. GSH kit was used to detect the expression of GSH in cells. The iron kit detected the total iron level and the expression level of ferric divalent ions in the cells. DCFH-DA fluorescent probe was used to detect ROS levels. Western blot was used to detect the expression of ferroptosis-related proteins in cells.Results: Pue alleviated LPS-induced injury and inflammatory response in A549 cells, and Pue reduced the expression of ROS, MDA and GSH in LPS-induced A549 cells. In addition, Pue reduced total iron levels and ferrous ion levels in LPS-induced A549 cells, and decreased the expression of iron ferroptosis-related proteins.Conclusion: Puerarin inhibited ferroptosis and inflammation of lung injury caused by sepsis in children in LPS induced lung epithelial cells.

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Section: Discussionmentioning

confidence: 99%

Puerarin Inhibits Ferroptosis and Inflammation of Lung Injury Caused by Sepsis in LPS Induced Lung Epithelial Cells

Wang

Chen

2021

Front. Pediatr.

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“…HMGB1 interacts with LPS to mediate caspase-11-dependent pyroptosis during endotoxin shock. These findings suggest that intracellular caspase-11 and GSDMD molecules [9,38], as well as LPS and HMGB1 in the blood, are the targets of endotoxin shock treatment [10,36,[47][48][49][50]. As discussed later, LPS and HMGB1 in the blood can be removed by blood purification.…”

Section: Lps-induced Vascular Endothelial Injurymentioning

confidence: 81%

“…However, it can also cause tissue damage, disseminated intravascular coagulation syndrome, organ failure, and death [34,35]. This novel intracellular LPS sensing pathway provides a new paradigm for LPS-triggered endotoxemia development, with potential implications for the pharmacological treatment of sepsis and septic shock [10,36].…”

Section: Lps Recognition Systemsmentioning

confidence: 99%

“…However, it was recently discovered that LPS not only acts extracellularly through TLR4, but also intracellularly through the activation of caspases/inflammasomes to induce inflammatory responses and cell death [6,7]. In addition, the mechanism of endotoxin internalization into cells from the blood has recently been clarified [8], and the significance of endotoxins in the blood has been of interest [9,10].…”

Section: Introductionmentioning

confidence: 99%

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Targeting Cytokines, Pathogen-Associated Molecular Patterns, and Damage-Associated Molecular Patterns in Sepsis via Blood Purification

Moriyama

Nishida

2021

IJMS

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Sepsis is characterized by a dysregulated immune response to infections that causes life-threatening organ dysfunction and even death. When infections occur, bacterial cell wall components (endotoxin or lipopolysaccharide), known as pathogen-associated molecular patterns, bind to pattern recognition receptors, such as toll-like receptors, to initiate an inflammatory response for pathogen elimination. However, strong activation of the immune system leads to cellular dysfunction and ultimately organ failure. Damage-associated molecular patterns (DAMPs), which are released by injured host cells, are well-recognized triggers that result in the elevation of inflammatory cytokine levels. A cytokine storm is thus amplified and sustained in this vicious cycle. Interestingly, during sepsis, neutrophils transition from powerful antimicrobial protectors into dangerous mediators of tissue injury and organ dysfunction. Thus, the concept of blood purification has evolved to include inflammatory cells and mediators. In this review, we summarize recent advances in knowledge regarding the role of lipopolysaccharides, cytokines, DAMPs, and neutrophils in the pathogenesis of sepsis. Additionally, we discuss the potential of blood purification, especially the adsorption technology, for removing immune cells and molecular mediators, thereby serving as a therapeutic strategy against sepsis. Finally, we describe the concept of our immune-modulating blood purification system.

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“…[34][35][36] In sepsis, there were also animal experiments for complement targeted therapy. Studies have shown that injecting C5a neutralizing antibodies into sepsis mice can greatly reduce the organ damage of mice and improve the survival rate of mice, 37 the original principle of this scheme was to block a large number of activated C5a from exerting biological functions, so whether this idea can be used for reference in C1q, this still needs more exploration.…”

mentioning

confidence: 99%

Serum C1q Levels Have Prognostic Value for Sepsis and are Related to the Severity of Sepsis and Organ Damage

Li¹,

Chen²,

Hu³

et al. 2021

JIR

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Objective To explore the clinical application value of serum complement component C1q levels in sepsis. Methods The clinical data and laboratory examination data of 320 research subjects (including 132 cases as sepsis group, 93 cases as nonsepsis group and 95 cases as control group) who were diagnosed and treated in Renmin Hospital of Wuhan University from July 2020 to March 2021 were collected. We compared the levels of each index among the three groups and further analyzed the C1q levels of different severity subgroups and different outcome subgroups of sepsis. Afterwards, we explored the correlation between C1q levels and SOFA score, organ damage indexes and coagulation indexes. Finally, the receiver operating characteristic curve (ROC) was used to analyze the prognostic value of C1q in patients with sepsis. Results C1q levels were significantly reduced in the serum of patients with sepsis; the level of C1q in the death group was lower than that in the survival group (127.1 mg/L vs 153.2 mg/L, P < 0.05), and the mortality in the C1q decreased group was higher when compared with C1q normal group; in addition, serum C1q levels were correlated with SOFA score, organ damage indexes and coagulation indexes; C1q had a high area under the curve (AUC) for the prognosis of sepsis, and the combination of other indexes can further improve the prognostic value. Conclusion Serum C1q levels have potential clinical value for the condition and prognosis of sepsis.

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Intracellular and Extracellular Lipopolysaccharide Signaling in Sepsis: Avenues for Novel Therapeutic Strategies

Cited by 90 publications

References 79 publications

Puerarin Inhibits Ferroptosis and Inflammation of Lung Injury Caused by Sepsis in LPS Induced Lung Epithelial Cells

Puerarin Inhibits Ferroptosis and Inflammation of Lung Injury Caused by Sepsis in LPS Induced Lung Epithelial Cells

Targeting Cytokines, Pathogen-Associated Molecular Patterns, and Damage-Associated Molecular Patterns in Sepsis via Blood Purification

Serum C1q Levels Have Prognostic Value for Sepsis and are Related to the Severity of Sepsis and Organ Damage

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