Glutathione Metabolism Is a Regulator of the Acute Inflammatory Response of Monocytes to (1→3)-β-D-Glucan

Ramendra, Rayoun; Mancini, Mathieu; Ayala, Jose-Mauricio; Tung, Lin Tze; Isnard, Stéphane; Lin, John; Routy, Jean‐Pierre; Nijnik, Anastasia; Langlais, David

doi:10.3389/fimmu.2021.694152

Cited by 8 publications

(5 citation statements)

References 51 publications

(78 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This activation can be inhibited with the Syk inhibitor piceatannol. It has also been shown that the exposure of myeloid cells to β-glucan modulates several cellular metabolic and epigenetic pathways that can induce cytokine production ( 72 ). Our data also suggest that elevation of specific microbiome-associated and inflammation-associated metabolic pathways may contribute to PASC, in particular, pathways with neurotoxic properties due to activation of NMDA receptors ( Figure 7 ).…”

Section: Discussionmentioning

confidence: 99%

“…This activates the NF-κB pathway and induces the secretion of proinflammatory cytokines (69)(70)(71). In addition, the exposure of myeloid cells to β-glucan can modulate several cellular metabolic (including glutathione metabolism) and epigenetic pathways that induce cytokine production (72). We, therefore, tested whether β-glucan levels correlated with markers of inflammation, as well as number of symptoms, and overall health/QoL score (Fig.…”

Section: Plasma β-Glucan Levels Associate With Markers Of Inflammatio...mentioning

confidence: 99%

See 1 more Smart Citation

Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling

Giron¹,

Peluso²,

Ding³

et al. 2022

JCI Insight

View full text Add to dashboard Cite

Long COVID, a type of Post-Acute Sequelae of SARS-CoV-2 (PASC), has been associated with sustained elevated levels of immune activation and inflammation. However, the mechanisms that drive this inflammation remain unknown. Inflammation during acute Coronavirus Disease 2019 could be exacerbated by microbial translocation (from gut and/or lung) to blood. Whether microbial translocation contributes to inflammation during PASC is unknown. We did not observe a significant elevation in plasma markers of bacterial translocation during PASC. However, we observed higher levels of fungal translocation -measured as β-glucan, a fungal cell wall polysaccharide -in the plasma of individuals experiencing PASC compared to those without PASC or SARS-CoV-2 negative controls.The higher β-glucan correlated with higher inflammation and elevated levels of host metabolites involved in activating N-Methyl-D-aspartate receptors (such as metabolites within the tryptophan catabolism pathway) with established neuro-toxic properties. Mechanistically, β-glucan can directly induce inflammation by binding to myeloid cells (via Dectin-1) and activating Syk/NF-κB signaling.Using a Dectin-1/NF-κB reporter model, we found that plasma from individuals experiencing PASC induced higher NF-κB signaling compared to plasma from negative controls. This higher NF-κB signaling was abrogated by Piceatannol (Syk inhibitor). These data suggest a potential targetable mechanism linking fungal translocation and inflammation during PASC.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Plasma β-Glucan Levels Associate With Markers Of Inflammatio...mentioning

confidence: 99%

Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling

Giron¹,

Peluso²,

Ding³

et al. 2022

JCI Insight

View full text Add to dashboard Cite

show abstract

“…Two pathways, starch and sucrose metabolism and androgen and estrogen biosynthesis, have been identified as important pathways in type 2 diabetes. 46 There were also several unique pathways related to oxidative stress, including glutathione metabolism, 52 vitamin A metabolism, 53 and vitamin B5 metabolism. 54 There were 12 unique pathways associated with PBB-153 in the F1 generation ( Figure 2 ; Figure S3).…”

Section: Discussionmentioning

confidence: 99%

Assessing Metabolic Differences Associated with Exposure to Polybrominated Biphenyl and Polychlorinated Biphenyls in the Michigan PBB Registry

Hoffman,

Liang,

Hood

et al. 2023

Environ Health Perspect

View full text Add to dashboard Cite

Background: Polybrominated biphenyls (PBB) and polychlorinated biphenyls (PCB) are persistent organic pollutants with potential endocrine-disrupting effects linked to adverse health outcomes. Objectives: In this study, we utilize high-resolution metabolomics (HRM) to identify internal exposure and biological responses underlying PCB and multigenerational PBB exposure for participants enrolled in the Michigan PBB Registry. Methods: HRM profiling was conducted on plasma samples collected from 2013 to 2014 from a subset of participants enrolled in the Michigan PBB Registry, including 369 directly exposed individuals (F0) who were alive when PBB mixtures were accidentally introduced into the food chain and 129 participants exposed to PBB in utero or through breastfeeding, if applicable (F1). Metabolome-wide association studies were performed for PBB-153 separately for each generation and (PCB-118, PCB-138, PCB-153, and PCB-180) in the two generations combined, as both had direct PCB exposure. Metabolite and metabolic pathway alterations were evaluated following a well-established untargeted HRM workflow. Results: Mean levels were [standard deviation (SD): 13.9] for PBB-153 and (SD: 0.788) for . Sixty-two and 26 metabolic features were significantly associated with PBB-153 in F0 and F1 [false discovery rate (FDR) ], respectively. There were 2,861 features associated with (FDR ). Metabolic pathway enrichment analysis using a bioinformatics tool revealed perturbations associated with in numerous oxidative stress and inflammation pathways (e.g., carnitine shuttle, glycosphingolipid, and vitamin B9 metabolism). Metabolic perturbations associated with PBB-153 in F0 were related to oxidative stress (e.g., pentose phosphate and vitamin C metabolism) and in F1 were related to energy production (e.g., pyrimidine, amino sugars, and lysine metabolism). Using authentic chemical standards, we confirmed the chemical identity of 29 metabolites associated with levels (level 1 evidence). Conclusions: Our results demonstrate that serum PBB-153 is associated with alterations in inflammation and oxidative stress-related pathways, which differed when stratified by generation. We also found that was associated with the downregulation of important neurotransmitters, serotonin, and 4-aminobutanoate. These findings provide novel insights for future investigations of molecular mechanisms underlying PBB and PCB exposure on health. https://doi.org/10.1289/EHP12657

show abstract

“…193 Also, pathogen-associated molecular patterns found in microorganisms (bacteria, fungi, viruses, and protozoa) that are engaged in the detection of pathogens may change the host immune cell's epigenetic environment. It has been shown by Ramendra et al 194 that the strong pathogen-associated molecular patterns of 1,3-D-glucan from fungus were able to modify the epigenetic landscape and chromatin accessibility of monocytes. 195 On the other hand, the HBV-encoded oncogene X protein of the hepatitis B virus can alter host miRNA patterns, which then modifies the viral burden and strengthens persistence.…”

Section: The Connection Between Infection and Epigeneticsmentioning

confidence: 99%

Expanding Role of Epigenetics in Human Health and Disease

Chakrabarti,

Chattopadhyay

2024

Explor Res Hypothesis Med

View full text Add to dashboard Cite

The traditional definition of epigenetics encompasses all molecular pathways that affect how a genotype expresses itself on the way to a particular phenotype, with epigenetics serving as the interface between genotype and phenotype. Unlike genetic changes, which may have protracted, irreversible effects on health and the emergence of illnesses, epigenetic modifications are reversible and do not change the DNA sequence. However, they can affect how our bodies interpret DNA sequences. Gene expression regulated by epigenetics has emerged as a major contributing element to the etiology of many diseases over time and a crucial determinant of human health. One of the strongest arguments in support of gene expression controlled by epigenetics comes from the startling discovery that DNA methylation causes X-chromosome inactivation, which has been connected to several diseases. The intrinsic uterine environment, where the embryo and fetus grow and develop over time to become neonates is vulnerable to early epigenetic settings throughout development, affecting the offspring's long-term health as well as their predisposition for different diseases. The epigenetic settings of germ cell development are influenced by environmental factors, which can result in transgenerational epigenetic effects. Therefore, in this article, we essentially provide a summary of the present level of understanding concerning the function of epigenetics regarding critical facets of human health, including in embryonic development and adulthood, with a particular emphasis on explaining the underlying diverse epigenetic mechanisms that regulate the onset of many human diseases, as well as cutting-edge technological tools used to study the human epigenome. Finally, we talk about the state of epigenetic therapies, which might be put to use in the treatment of a range of human diseases.

show abstract

Glutathione Metabolism Is a Regulator of the Acute Inflammatory Response of Monocytes to (1→3)-β-D-Glucan

Cited by 8 publications

References 51 publications

Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling

Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling

Assessing Metabolic Differences Associated with Exposure to Polybrominated Biphenyl and Polychlorinated Biphenyls in the Michigan PBB Registry

Expanding Role of Epigenetics in Human Health and Disease

Contact Info

Product

Resources

About