Ceramide in apoptosis and oxidative stress in allergic inflammation and asthma

James, Briana N.; Oyeniran, Clément; Sturgill, Jamie; Newton, Jason; Martin, Rebecca; Bieberich, Erhard; Weigel, Cynthia; Maczis, Melissa A.; Palladino, Elisa N.D.; Lownik, Joseph C.; Trudeau, John B.; Cook‐Mills, Joan M.; Wenzel, Sally E.; Milstien, Sheldon; Spiegel, Sarah

doi:10.1016/j.jaci.2020.10.024

Cited by 45 publications

(40 citation statements)

References 72 publications

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“…Lipid metabolites regulate DC differentiation/function (26)(27)(28)(29), and DCs mediate initiation of allergic disease (4,12). It is reported that βGalCer is required for hematopoiesis (67) and that ceramide is elevated in allergic non-pregnant female mice (68). In our studies, βGalCer and ceramide was present but not elevated in the allergic mothers and their offspring.…”

Section: Discussionsupporting

confidence: 47%

β-Glucosylceramide From Allergic Mothers Enhances Offspring Responsiveness to Allergen

et al. 2021

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In animals and humans, offspring of allergic mothers have increased responsiveness to allergen and the allergen-specificity of the offspring can be different than that of the mother. In our preclinical models, the mother's allergic responses influence development of the fetus and offspring by elevating numbers of cells in dendritic cell subsets. A major question is the identity of maternal factors of allergic mothers that alter offspring development of responsiveness to allergen. Lipids are altered during allergic responses and lipids are transported to the fetus for growth and formation of fetal membranes. We hypothesized that pro-inflammatory lipids, that are elevated in allergic mothers, are transported to the fetus and regulate fetal immune development. We demonstrate in this report that there was a significant 2-fold increase in β-glucosylceramides (βGlcCer) in allergic mothers, the fetal liver and her offspring. The βGlcCer were transported from mother's plasma, across the placenta, to the fetus and in breastmilk to the offspring. Administration of βGlcCer to non-allergic mothers was sufficient for offspring responses to allergen. Importantly, maternal administration of a clinically relevant pharmacological inhibitor of βGlcCer synthase returned βGlcCer to normal levels in the allergic mothers and her offspring and blocked the offspring increase in dendritic cell subsets and offspring allergen responsiveness. In summary, allergic mothers had increased βGlcCer that was transported to offspring and mediated increases in offspring DCs and responsiveness to allergen. These data have a significant impact on our understanding of mechanisms for development of allergies in offspring of allergic mothers and have the potential to lead to novel interventions that significantly impact risk for allergic disease early in life.

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Section: Discussionsupporting

confidence: 47%

β-Glucosylceramide From Allergic Mothers Enhances Offspring Responsiveness to Allergen

et al. 2021

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“…An increase in C1P along with a decrease in S1P induces cell death pathways, while the opposite scenario results in the stimulation of anti-apoptotic pathways (8,12,(15)(16)(17)(18). C1P is related to caspase-3-mediated apoptosis and cell cycle arrest while S1P is related to proliferation and survival (19,20).…”

Section: Sphingolipidsmentioning

confidence: 99%

The Role of Sphingolipids in Allergic Disorders

et al. 2021

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Allergy is defined as a complex chronic inflammatory condition in which genetic and environmental factors are implicated. Sphingolipids are involved in multiple biological functions, from cell membrane components to critical signaling molecules. To date, sphingolipids have been studied in different human pathologies such as neurological disorders, cancer, autoimmunity, and infections. Sphingolipid metabolites, in particular, ceramide and sphingosine-1-phosphate (S1P), regulate a diverse range of cellular processes that are important in immunity and inflammation. Moreover, variations in the sphingolipid concentrations have been strongly associated with allergic diseases. This review will focus on the role of sphingolipids in the development of allergic sensitization and allergic inflammation through the activation of immune cells resident in tissues, as well as their role in barrier remodeling and anaphylaxis. The knowledge gained in this emerging field will help to develop new therapeutic options for allergic disorders.

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“…Oxidative stress exacerbates lipid peroxidation, protein misfolding and dysfunction [5], DNA damage [6], and organelle stress [7] like mitochondria or endoplasmic reticulum (ER) to accelerate defective cell differentiation and cell apoptosis or necrosis. In addition, oxidative stress and subsequent apoptosis are critical in the development of oxidative stress-associated disorders and become the target of therapeutic interventions [8][9][10]. Similarly, in periodontitis, the hypoxic subgingival environment triggering aberrant apoptosis would contribute to the pathogenesis by enabling persistent infection and aggravating host immune responses, which would cause an imbalance between resorption destruction and mineralization reconstruction of periodontal tissue [11].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of TRPA1 Ameliorates Periodontitis by Reducing Periodontal Ligament Cell Oxidative Stress and Apoptosis via PERK/eIF2α/ATF-4/CHOP Signal Pathway

Liu

Guo

Huang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Objective. In periodontitis, excessive oxidative stress combined with subsequent apoptosis and cell death further exacerbated periodontium destruction. TRPA1, an important transient receptor potential (TRP) cation channel, may participate in the process. This study is aimed at exploring the role and the novel therapeutic function of TRPA1 in periodontitis. Methods. Periodontal ligament cells or tissues derived from healthy and periodontitis (PDLCs/Ts and P-PDLCs/Ts) were used to analyze the oxidative and apoptotic levels and TRPA1 expression. TRPA1 inhibitor (HC030031) was administrated in inflammation induced by P. gingivalis lipopolysaccharide (P.g.LPS) to investigate the oxidative and apoptotic levels of PDLCs. The morphology of the endoplasmic reticulum (ER) and mitochondria was identified by transmission electron microscope, and the PERK/eIF2α/ATF-4/CHOP signal pathways were detected. Finally, HC030031 was administered to periodontitis mice to evaluate its effect on apoptotic and oxidative levels in the periodontium and the relieving of periodontitis. Results. The oxidative, apoptotic levels and TRPA1 expression were higher in P-PDLC/Ts from periodontitis patients and in P.g.LPS-induced inflammatory PDLCs. TRPA1 inhibitor significantly decreased the intracellular calcium, oxidative stress, and apoptosis of inflammatory PDLCs and decreased ER stress by downregulating PERK/eIF2α/ATF-4/CHOP pathways. Meanwhile, the overall calcium ion decrease induced by EGTA also exerted similar antiapoptosis and antioxidative stress functions. In vivo, HC030031 significantly reduced oxidative stress and apoptosis in the gingiva and periodontal ligament, and less periodontium destruction was observed. Conclusion. TRPA1 was highly related to periodontitis, and TRPA1 inhibitor significantly reduced oxidative and apoptotic levels in inflammatory PDLCs via inhibiting ER stress by downregulating PERK/eIF2α/ATF-4/CHOP pathways. It also reduced the oxidative stress and apoptosis in periodontitis mice thus ameliorating the development of periodontitis.

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Ceramide in apoptosis and oxidative stress in allergic inflammation and asthma

Cited by 45 publications

References 72 publications

β-Glucosylceramide From Allergic Mothers Enhances Offspring Responsiveness to Allergen

β-Glucosylceramide From Allergic Mothers Enhances Offspring Responsiveness to Allergen

The Role of Sphingolipids in Allergic Disorders

Inhibition of TRPA1 Ameliorates Periodontitis by Reducing Periodontal Ligament Cell Oxidative Stress and Apoptosis via PERK/eIF2α/ATF-4/CHOP Signal Pathway

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