Thiosulfinate-Enriched Allium sativum Extract Exhibits Differential Effects between Healthy and Sepsis Patients: The Implication of HIF-1α

Avendaño-Ortíz, José; Redondo‐Calvo, Francisco Javier; Lozano-Rodríguez, Roberto; Terrón-Arcos, Verónica; Bergón-Gutiérrez, Marta; Rodríguez-Jiménez, Concepción; Rodríguez, Juan F.; Campo, Rosa del; Gómez, Luis Alfonso Escudero; Bejarano-Ramírez, Natalia; Pérez‐Ortiz, José Manuel; López‐Collazo, Eduardo

doi:10.3390/ijms24076234

Cited by 3 publications

(2 citation statements)

References 45 publications

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“…This becomes flawless in the differential impact of garlic-derived extracts on the memory phenotype observed between monocytes from healthy volunteers and septic patients. This extract induced ET in healthy volunteers while boosted inflammatory responses were observed in septic patients, in a HIF1α-dependent manner ( 132 ).…”

Section: Tolerance Versus Training Similarities An...mentioning

confidence: 99%

Endotoxin tolerance and trained immunity: breaking down immunological memory barriers

López-Collazo,

del Fresno

2024

Front. Immunol.

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For decades, innate immune cells were considered unsophisticated first responders, lacking the adaptive memory of their T and B cell counterparts. However, mounting evidence demonstrates the surprising complexity of innate immunity. Beyond quickly deploying specialized cells and initiating inflammation, two fascinating phenomena – endotoxin tolerance (ET) and trained immunity (TI) – have emerged. ET, characterized by reduced inflammatory response upon repeated exposure, protects against excessive inflammation. Conversely, TI leads to an enhanced response after initial priming, allowing the innate system to mount stronger defences against subsequent challenges. Although seemingly distinct, these phenomena may share underlying mechanisms and functional implications, blurring the lines between them. This review will delve into ET and TI, dissecting their similarities, differences, and the remaining questions that warrant further investigation.

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Section: Tolerance Versus Training Similarities An...mentioning

confidence: 99%

Endotoxin tolerance and trained immunity: breaking down immunological memory barriers

López-Collazo,

del Fresno

2024

Front. Immunol.

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“…A deeper understanding of the biology of monocytes in sepsis may reveal new therapeutic strategies to modulate their activity [ 17 ]. The bidirectional nature of monocytes in promoting inflammation and resolution and repair emphasizes the need to elucidate the regulatory networks influencing their function [ 18 ]. Despite extensive research on various signaling pathways, such as NF-κB and STAT, exploring alternative pathways regulating monocyte responses in sepsis remains a crucial research area [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Plac8-ERK pathway modulation of monocyte function in sepsis

Zhang,

Fu,

Chen

et al. 2024

Cell Death Discov.

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Sepsis, a life-threatening condition caused by infection, is characterized by the dysregulation of immune responses and activation of monocytes. Plac8, a protein, has been implicated in various inflammatory conditions. This study aimed to investigate the effect of Plac8 upregulation on monocyte proliferation and activation in sepsis patients. Peripheral blood samples were collected from healthy individuals and sepsis patients. Monocytes were stimulated with lipopolysaccharide (LPS) to create an in vitro sepsis model, while a murine sepsis model was established using cecal ligation and puncture (CLP). The levels of monocyte markers, proliferation index (PI), and pro-inflammatory cytokines were assessed using flow cytometry and qPCR, respectively. Plac8 and phosphorylated ERK protein levels were determined by western blot, and TNF-α, IL-6, and IL-10 levels were quantified using ELISA. The CCK-8 assay was used to evaluate PBMC proliferation and activation. The results showed that Plac8 was highly expressed in sepsis models, promoting the survival, proliferation, and activation of monocytes. Plac8 upregulation activated the ERK pathway, leading to increased phosphorylation of ERK protein and elevated levels of CD14, CD16, TNF-α, IL-6, Plac8, and IL-10. In sepsis mice, Plac8 overexpression similarly activated the ERK pathway and promoted the survival, proliferation, and activation of monocytes. In conclusion, the upregulation of Plac8 enhances the activation of the ERK pathway and promotes monocyte proliferation and activation in sepsis patients.

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Unraveling the role of HIF-1α in sepsis: from pathophysiology to potential therapeutics—a narrative review

Ruan,

Zhang,

Zhang

et al. 2024

Crit Care

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Sepsis is characterized by organ dysfunction resulting from a dysregulated inflammatory response triggered by infection, involving multifactorial and intricate molecular mechanisms. Hypoxia-inducible factor-1α (HIF-1α), a notable transcription factor, assumes a pivotal role in the onset and progression of sepsis. This review aims to furnish a comprehensive overview of HIF-1α's mechanism of action in sepsis, scrutinizing its involvement in inflammatory regulation, hypoxia adaptation, immune response, and organ dysfunction. The review encompasses an analysis of the structural features, regulatory activation, and downstream signaling pathways of HIF-1α, alongside its mechanism of action in the pathophysiological processes of sepsis. Furthermore, it will delve into the roles of HIF-1α in modulating the inflammatory response, including its association with inflammatory mediators, immune cell activation, and vasodilation. Additionally, attention will be directed toward the regulatory function of HIF-1α in hypoxic environments and its linkage with intracellular signaling, oxidative stress, and mitochondrial damage. Finally, the potential therapeutic value of HIF-1α as a targeted therapy and its significance in the clinical management of sepsis will be discussed, aiming to serve as a significant reference for an in-depth understanding of sepsis pathogenesis and potential therapeutic targets, as well as to establish a theoretical foundation for clinical applications. Graphical Abstract

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Thiosulfinate-Enriched Allium sativum Extract Exhibits Differential Effects between Healthy and Sepsis Patients: The Implication of HIF-1α

Cited by 3 publications

References 45 publications

Endotoxin tolerance and trained immunity: breaking down immunological memory barriers

Endotoxin tolerance and trained immunity: breaking down immunological memory barriers

Plac8-ERK pathway modulation of monocyte function in sepsis

Unraveling the role of HIF-1α in sepsis: from pathophysiology to potential therapeutics—a narrative review

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