Endotoxin in Sepsis: Methods for LPS Detection and the Use of Omics Techniques

Virzì, Grazia Maria; Mattiotti, Maria; Cal, Massimo de; Ronco, Claudio; Zanella, Monica; Rosa, Silvia De

doi:10.3390/diagnostics13010079

Cited by 23 publications

(13 citation statements)

References 84 publications

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“…While the local acute inflammation helps to combat the infection, an excessive response to the infection leads to sepsis with a potentially fatal outcome. On the other hand, a prolonged low-grade inflammation contributes to the development of type 2 diabetes, cardiovascular disease, and other diseases [ 3 , 4 ]. Such chronic inflammation is potentiated by the activity of cytoplasmic NLRP3 inflammasome which can be activated downstream of TLR4 signaling [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Flotillins affect LPS-induced TLR4 signaling by modulating the trafficking and abundance of CD14

Matveichuk,

Ciesielska,

Hromada-Judycka

et al. 2024

Cell. Mol. Life Sci.

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Lipopolysaccharide (LPS) induces a strong pro-inflammatory reaction of macrophages upon activation of Toll-like receptor 4 (TLR4) with the assistance of CD14 protein. Considering a key role of plasma membrane rafts in CD14 and TLR4 activity and the significant impact exerted on that activity by endocytosis and intracellular trafficking of the both LPS acceptors, it seemed likely that the pro-inflammatory reaction could be modulated by flotillins. Flotillin-1 and -2 are scaffolding proteins associated with the plasma membrane and also with endo-membranes, affecting both the plasma membrane dynamics and intracellular protein trafficking. To verify the above hypothesis, a set of shRNA was used to down-regulate flotillin-2 in Raw264 cells, which were found to also become deficient in flotillin-1. The flotillin deficiency inhibited strongly the TRIF-dependent endosomal signaling of LPS-activated TLR4, and to a lower extent also the MyD88-dependent one, without affecting the cellular level of TLR4. The flotillin depletion also inhibited the pro-inflammatory activity of TLR2/TLR1 and TLR2/TLR6 but not TLR3. In agreement with those effects, the depletion of flotillins down-regulated the CD14 mRNA level and the cellular content of CD14 protein, and also inhibited constitutive CD14 endocytosis thereby facilitating its shedding. Ultimately, the cell-surface level of CD14 was markedly diminished. Concomitantly, CD14 recycling was enhanced via EEA1-positive early endosomes and golgin-97-positive trans-Golgi network, likely to compensate for the depletion of the cell-surface CD14. We propose that the paucity of surface CD14 is the reason for the down-regulated signaling of TLR4 and the other TLRs depending on CD14 for ligand binding. Graphical abstract

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Section: Introductionmentioning

confidence: 99%

Flotillins affect LPS-induced TLR4 signaling by modulating the trafficking and abundance of CD14

Matveichuk,

Ciesielska,

Hromada-Judycka

et al. 2024

Cell. Mol. Life Sci.

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“…Polymyxin-B-coated polystyrene fibers have been included in a special adsorption cartridge (Toraymyxin, Toray, Japan) and are capable of removal of circulating endotoxin up to approximately 20 μg in a two-hour treatment. [31][32][33] The controversial results achieved so far in studies involving extracorporeal hemoadsorption with Toraymyxin [34,35] could be attributable to the remarkable heterogeneity of the treated populations in different studies. [30,36] Analyses have demonstrated that positive results are more likely in patients with significant organ failure and in patients with endotoxin activity between 0.6 and 0.9.…”

Section: The Case Of the Critically Ill Patient With Sepsis Or Sa-akimentioning

confidence: 99%

Which Patient Phenotype Is the Ideal Candidate for Hemoadsorption in Acute and Chronic Kidney Disease?

Ronco,

Kellum

2024

Integr Med Nephrol Androl

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“…Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection [7]. Its pathogenesis includes various steps, such as infection, hyperactivation of the immune system, endothelial dysfunction leading to loss of barrier integrity, followed by tissue damage, and finally, multi-organ failure and death [8] (Figure 1).…”

Section: Sepsismentioning

confidence: 99%

Dose-Dependent Effects of Lipopolysaccharide on the Endothelium—Sepsis versus Metabolic Endotoxemia-Induced Cellular Senescence

Merk,

Cox,

Jakobs

et al. 2024

Antioxidants

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The endothelium, the innermost cell layer of blood vessels, is not only a physical barrier between the bloodstream and the surrounding tissues but has also essential functions in vascular homeostasis. Therefore, it is not surprising that endothelial dysfunction is associated with most cardiovascular diseases. The functionality of the endothelium is compromised by endotoxemia, the presence of bacterial endotoxins in the bloodstream with the main endotoxin lipopolysaccharide (LPS). Therefore, this review will focus on the effects of LPS on the endothelium. Depending on the LPS concentration, the outcomes are either sepsis or, at lower concentrations, so-called low-dose or metabolic endotoxemia. Sepsis, a life-threatening condition evoked by hyperactivation of the immune response, includes breakdown of the endothelial barrier resulting in failure of multiple organs. A deeper understanding of the underlying mechanisms in the endothelium might help pave the way to new therapeutic options in sepsis treatment to prevent endothelial leakage and fatal septic shock. Low-dose endotoxemia or metabolic endotoxemia results in chronic inflammation leading to endothelial cell senescence, which entails endothelial dysfunction and thus plays a critical role in cardiovascular diseases. The identification of compounds counteracting senescence induction in endothelial cells might therefore help in delaying the onset or progression of age-related pathologies. Interestingly, two natural plant-derived substances, caffeine and curcumin, have shown potential in preventing endothelial cell senescence.

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Endotoxin in Sepsis: Methods for LPS Detection and the Use of Omics Techniques

Cited by 23 publications

References 84 publications

Flotillins affect LPS-induced TLR4 signaling by modulating the trafficking and abundance of CD14

Flotillins affect LPS-induced TLR4 signaling by modulating the trafficking and abundance of CD14

Which Patient Phenotype Is the Ideal Candidate for Hemoadsorption in Acute and Chronic Kidney Disease?

Dose-Dependent Effects of Lipopolysaccharide on the Endothelium—Sepsis versus Metabolic Endotoxemia-Induced Cellular Senescence

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