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Reprogramming of pro-inflammatory human macrophages to an anti-inflammatory phenotype by bile acids

ABSTRACT: Reprogramming of pro-inflammatory human macrophages to an anti-inflammatory phenotype by bile acids

PROVIDER: PRJNA814644 | ENA |

REPOSITORIES: ENA

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Reprogramming of pro-inflammatory human macrophages to an anti-inflammatory phenotype by bile acids

Project description:Cholestasis is caused by autoimmune reactions, drug-induced hepatotoxicity, viral infections of the liver and the obstruction of bile ducts by tumours or gallstones. Cholestatic conditions are associated with impaired innate and adaptive immunity, including alterations of the cellular functions of monocytes, macrophages, NK cells and T-cells. Bile acids act as signalling molecules, affecting lipopolysaccharide (LPS)-induced cytokine expression in primary human macrophages. The present manuscript investigates the impact of bile acids, such as taurolithocholic acid (TLC), on the transcriptome of human macrophages in the presence or absence of LPS. While TLC itself has almost no effect on gene expression under control conditions, this compound modulates the expression of 202 out of 865 transcripts in the presence of LPS. Interestingly, pathway analysis revealed that TLC specifically supressed the expression of genes involved in mediating pro-inflammatory effects, phagocytosis, interactions with pathogens and autophagy as well as the recruitment of immune cells, such as NK cells, neutrophils and T cells. These data indicate a broad influence of bile acids on inflammatory responses and immune functions in macrophages. These findings may contribute to the clinical observation that patients with cholestasis present a lack of response to bacterial or viral infections.

2022-03-11 | GSE198326 | GEO

Deoxyhypusine Synthase Promotes a Pro-Inflammatory Macrophage Phenotype

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Reprogramming of pro-inflammatory human macrophages to an anti-inflammatory phenotype by bile acids.

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Pro-inflammatory monocyte phenotype during acute progression of cerebral small vessel disease

Project description:The aetiology of cerebral small vessel disease (SVD) remains elusive, though currently evidence is accumulating that inflammation contributes to its pathophysiology. In this prospective high-frequency imaging study, we showed that the incidence of acute SVD progression coincides with a functional and transcriptional pro-inflammatory monocyte phenotype. To detect SVD progression, individuals with SVD underwent monthly magnetic resonance imaging (MRI) for 10 consecutive months. RNA sequencing revealed a pro-inflammatory monocyte signature with upregulation of the EGR2 gene. Collectively, we showed that individuals with progressive SVD have pro-inflammatory circulating monocytes characterized by an augmented cytokine production capacity and a pro-inflammatory transcriptional signature.

2020-12-09 | GSE162790 | GEO

Pro-inflammatory monocyte phenotype during acute progression of cerebral small vessel disease

Project description:Pro-inflammatory monocyte phenotype during acute progression of cerebral small vessel disease

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Differential view on the bile acids stress response of Clostridioides difficile

Project description:In this study, we aimed at the characterization of C. difficile’s stress response to the main four human bile acids. Although, a phenotypically description of growth differences upon challenge with different bile acids has been described (Lewis 2016, Thanissery 2017), there is no information on the adaptation of gene expression available. We employed a comprehensive proteomics approach to record stress signatures of the unconjugated bile acids CA, CDCA, DCA and LCA in shock experiments as well as during long-term-stress conditions and could depict a general stress response concerning all four bile acids, but also specific responses to only a single or a few of the different bile acids. Our results are a starting point for the understanding of how the individual bile acids cocktail of a patient can decide on the outcome of a C. difficile infection.

2019-02-12 | PXD010514 | Pride

Differential view on the bile acids stress response of Clostridioides difficile_longterm stress

Project description:In this study, we aimed at the characterization of C. difficile’s stress response to the main four human bile acids. Although, a phenotypically description of growth differences upon challenge with different bile acids has been described (Lewis 2016, Thanissery 2017), there is no information on the adaptation of gene expression available. We employed a comprehensive proteomics approach to record stress signatures of the unconjugated bile acids CA, CDCA, DCA and LCA during long-term-stress conditions and could depict a general stress response concerning all four bile acids, but also specific responses to only a single or a few of the different bile acids. Our results are a starting point for the understanding of how the individual bile acids cocktail of a patient can decide on the outcome of a C. difficile infection

2019-02-09 | PXD010525 | Pride

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