Sphingomyelin synthase activity affects TRIF-dependent signaling of Toll-like receptor 4 in cells stimulated with lipopolysaccharide

Prymas, Kamila; Świątkowska, Anna; Traczyk, Gabriela; Ziemlińska, Ewelina; Dziewulska, Anna; Ciesielska, Anna; Kwiatkowska, Katarzyna

doi:10.1016/j.bbalip.2019.158549

Cited by 16 publications

(13 citation statements)

References 76 publications

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“…Only scarce data allow speculation on the pathway(s) involved in the internalization of CD14 carrying LPS and other ligands, like oxPAPC, and also in the constitutivie endocytosis of CD14 in resting murine macrophages [17]. The latter is of importance since a down-regulation the cell surace level of CD14 and TLR4 in resting cells should prevent excessive LPS-induced pro-inflammatory signaling of TLR4 [161,210]. This mechanism can also contribute to the antagonistic activity of R. spheroides LPS toward human and murine TLR4.…”

Section: Cellular Trafficking Of Cd14 and Its Relation To The Trafficmentioning

confidence: 99%

TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling

Ciesielska

Matyjek

Kwiatkowska

2020

Cell. Mol. Life Sci.

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711

466

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Toll-like receptor (TLR) 4 belongs to the TLR family of receptors inducing pro-inflammatory responses to invading pathogens. TLR4 is activated by lipopolysaccharide (LPS, endotoxin) of Gram-negative bacteria and sequentially triggers two signaling cascades: the first one involving TIRAP and MyD88 adaptor proteins is induced in the plasma membrane, whereas the second engaging adaptor proteins TRAM and TRIF begins in early endosomes after endocytosis of the receptor. The LPS-induced internalization of TLR4 and hence also the activation of the TRIF-dependent pathway is governed by a GPI-anchored protein, CD14. The endocytosis of TLR4 terminates the MyD88-dependent signaling, while the following endosome maturation and lysosomal degradation of TLR4 determine the duration and magnitude of the TRIF-dependent one. Alternatively, TLR4 may return to the plasma membrane, which process is still poorly understood. Therefore, the course of the LPS-induced pro-inflammatory responses depends strictly on the rates of TLR4 endocytosis and trafficking through the endo-lysosomal compartment. Notably, prolonged activation of TLR4 is linked with several hereditary human diseases, neurodegeneration and also with autoimmune diseases and cancer. Recent studies have provided ample data on the role of diverse proteins regulating the functions of early, late, and recycling endosomes in the TLR4-induced inflammation caused by LPS or phagocytosis of E. coli. In this review, we focus on the mechanisms of the internalization and intracellular trafficking of TLR4 and CD14, and also of LPS, in immune cells and discuss how dysregulation of the endo-lysosomal compartment contributes to the development of diverse human diseases.

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Section: Cellular Trafficking Of Cd14 and Its Relation To The Trafficmentioning

confidence: 99%

TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling

Ciesielska

Matyjek

Kwiatkowska

2020

Cell. Mol. Life Sci.

Self Cite

711

466

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“…Plasma membrane rafts of resting cells are now considered to be extremely labile nanometer-sized structures formed due to interactions of sphingolipids and cholesterol, with a contribution of cell-surface GPI-anchored proteins and S-palmitoylated transmembrane/peripheral proteins and their oligomerization. These dynamic nanodomains can merge together upon cell stimulation into more stable platforms, thereby causing local accumulation of distinct receptors, proteins engaged in their signaling pathways, and lipids involved in these signaling cascades, such as sphingolipids and phosphatidylinositols [82,88,[96][97][98][99][100][101].…”

Section: Association Of Flotillins With Rafts Facilitates Endocytosismentioning

confidence: 99%

Flotillins: At the Intersection of Protein S-Palmitoylation and Lipid-Mediated Signaling

Kwiatkowska

Matveichuk

Fronk

et al. 2020

IJMS

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Flotillin-1 and flotillin-2 are ubiquitously expressed, membrane-associated proteins involved in multifarious cellular events from cell signaling, endocytosis, and protein trafficking to gene expression. They also contribute to oncogenic signaling. Flotillins bind the cytosolic leaflet of the plasma membrane and endomembranes and, upon hetero-oligomerization, serve as scaffolds facilitating the assembly of multiprotein complexes at the membrane–cytosol interface. Additional functions unique to flotillin-1 have been discovered recently. The membrane-binding of flotillins is regulated by S-palmitoylation and N-myristoylation, hydrophobic interactions involving specific regions of the polypeptide chain and, to some extent, also by their oligomerization. All these factors endow flotillins with an ability to associate with the sphingolipid/cholesterol-rich plasma membrane domains called rafts. In this review, we focus on the critical input of lipids to the regulation of the flotillin association with rafts and thereby to their functioning. In particular, we discuss how the recent developments in the field of protein S-palmitoylation have contributed to the understanding of flotillin1/2-mediated processes, including endocytosis, and of those dependent exclusively on flotillin-1. We also emphasize that flotillins affect directly or indirectly the cellular levels of lipids involved in diverse signaling cascades, including sphingosine-1-phosphate and PI(4,5)P2. The mutual relations between flotillins and distinct lipids are key to the regulation of their involvement in numerous cellular processes.

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“…• Promotes NF-κB activation, CCL5 expression, and recruitment of CD14, TLR4, and TNF receptors to the cell membrane in macrophages 92,93 • Long-chain and very-long-chain SM levels correlate to increased levels of inflammatory cytokines in atherosclerotic plaques 94,95 • Protects against cigarette smoke-induced airway inflammation and is associated with reduced risk for emphysema 96,97 In MSCs • In BM-MSCs, SM levels increase with aging and promote senescence 98…”

Section: Inflammationmentioning

confidence: 99%

Characterizing Human Mesenchymal Stromal Cells Immune Modulatory Potency Using Targeted Lipidomic Profiling of Sphingolipids

DeVeaux

Vyshnya

et al. 2021

Preprint

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Cell therapies are expected to increase over the next decade due to increasing demand for clinical applications. Mesenchymal stromal cells (MSCs) have been explored to treat a number of diseases, with some successes in early clinical trials. Despite early successes, poor MSC characterization results in lessened therapeutic capacity once in vivo. Here, we characterized bone marrow (BM), adipose derived and umbilical cord tissue MSCs sphingolipids (SLs), a class of bioactive lipids, using liquid chromatography tandem mass spectrometry. We found ceramide levels differed based upon donors sex in BM MSCs. We detected fatty acyl chain variants in MSCs from all 3 sources. Principal component analysis showed IFNg; primed and untreated MSCs separated according to their SL signature. We detected higher ceramide levels in low IDO MSCs, indicating sphingomeylinase or ceramidase enzymatic activity may be involved in their immune potency. Lastly, linear discriminant analysis revealed that MSCs separated based on tissue source.

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Sphingomyelin synthase activity affects TRIF-dependent signaling of Toll-like receptor 4 in cells stimulated with lipopolysaccharide

Cited by 16 publications

References 76 publications

TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling

TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling

Flotillins: At the Intersection of Protein S-Palmitoylation and Lipid-Mediated Signaling

Characterizing Human Mesenchymal Stromal Cells Immune Modulatory Potency Using Targeted Lipidomic Profiling of Sphingolipids

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