Effects of anti-inflammatory drugs on the expression of tryptophan-metabolism genes by human macrophages

Regan, Tim; Gill, Andrew C.; Clohisey, Sara; Barnett, Mark W.; Pariante, Carmine M.; Harrison, Neil A.; Hume, David; Bullmore, Edward T.; Freeman, Tom C.

doi:10.1002/jlb.3a0617-261r

Cited by 23 publications

(21 citation statements)

References 70 publications

(166 reference statements)

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“…This degradative pathway lowers the immune response through producing various molecules in the kynurenine pathway, including kynurenine, which can bind to the aryl hydrocarbon receptor (AHR) receptor causing immune suppression [67,68]. Regan et al reported depletion in tryptophan with an accumulation of kynurenine following stimulation by LPS and IFN-α [69,70]. The anti-inflammatory drug indomethacin caused a significant attenuation of the effects of LPS on tryptophan and a reduction in the level of kynurenine was observed following IFN-α stimulation, but no effect on kynurenine was observed after LPS treatment [70].…”

Section: Discussionmentioning

confidence: 99%

Propolis Exerts an Anti-Inflammatory Effect on PMA-Differentiated THP-1 Cells via Inhibition of Purine Nucleoside Phosphorylase

et al. 2019

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Previous research has shown that propolis has immunomodulatory activity. Propolis extracts from different geographic origins were assessed for their anti-inflammatory activities by investigating their ability to alter the production of tumour necrosis factor-α (TNF-α) and the cytokines interleukin-1β (IL-1β), IL-6 and IL-10 in THP-1-derived macrophage cells co-stimulated with lipopolysaccharide (LPS). All the propolis extracts suppressed the TNF-α and IL-6 LPS-stimulated levels. Similar suppression effects were detected for IL-1β, but the release of this cytokine was synergised by propolis samples from Ghana and Indonesia when compared with LPS. Overall, the Cameroonian propolis extract (P-C) was the most active and this was evaluated for its effects on the metabolic profile of unstimulated macrophages or macrophages activated by LPS. The levels of 81 polar metabolites were identified by liquid chromatography (LC) coupled with mass spectrometry (MS) on a ZIC-pHILIC column. LPS altered the energy, amino acid and nucleotide metabolism in THP-1 cells, and interpretation of the metabolic pathways showed that P-C reversed some of the effects of LPS. Overall, the results showed that propolis extracts exert an anti-inflammatory effect by inhibition of pro-inflammatory cytokines and by metabolic reprogramming of LPS activity in macrophage cells, suggesting an immunomodulatory effect.

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Section: Discussionmentioning

confidence: 99%

Propolis Exerts an Anti-Inflammatory Effect on PMA-Differentiated THP-1 Cells via Inhibition of Purine Nucleoside Phosphorylase

et al. 2019

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“…3). We put together four purified human macrophage datasets: (GSE35449, n=21) 25 , (GSE85333, n=185) 26 , (GSE46903, n=384) 27 , (GSE55536, n=33) 28 , and four diverse mouse macrophage datasets: (GSE82158, n=163) 29 , (GSE38705, n=511) 30 , (GSE62420, n=56) 31 , and (GSE86397, n=12) 32 .…”

Section: Resultsmentioning

confidence: 99%

“…We put together four purified human macrophage datasets: (GSE35449, n=21) 25 , (GSE85333, n=185) 26 , (GSE46903, n=384) 27 , (GSE55536, n=33) 28 .…”

Section: Methodsmentioning

confidence: 99%

Computational approach to identifying universal macrophage biomarker

Dang

Taheri

Das

et al. 2019

Preprint

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ABSTRACTMacrophages are a type of white blood cell, of the immune system, that engulfs and digests cellular debris, cancer cells, and anything else that does not have the type of proteins specific to healthy body cells on its surface. Understanding gene expression dynamics in macrophages are crucial for studying human diseases. Recent advances in high-throughput technologies have enabled the collection of immense amounts of biological data. A reliable marker of macrophage is essential to study their function. Traditional approaches use a number of markers that may have tissue specific expression patterns. To identify universal biomarker of macrophage, we used a previously published computational approach called BECC (Boolean Equivalent Correlated Clusters) that was originally used to identify universal cell cycle genes. We performed BECC analysis on a seed gene CD14, a known macrophage marker. FCER1G and TYROBP were among the top candidates which were validated as strong candidates for universal biomarkers for macrophages in human and mouse tissues. To our knowledge, such a finding is first of its kind.CONTRIBUTIONS TO THE FIELDWe have developed a computational approach to identify universal biomarkers of different entities in a biological system. We applied this approach to study macrophages and identified universal biomarkers of this particular cell type. FCER1G and TYROBP were among the top candidates which were validated as strong candidates for universal biomarkers for macrophages in human and mouse tissues. The expression patterns of TYROBP and FCER1G are found to be more homogeneous compared to currently used biomarkers such as ITGAM, EMR1 (F4/80), and CD68. Further, we demonstrated that this homogeneity extends to all the tissues currently profiled in the public domain in multiple species including human and mouse. FCER1G and TYROBP expression patterns were also found to be extremely specific to macrophages found in various tissues. They are strongly co-expressed together. We believe that these two genes are the most reliable candidates of universal biomarker for macrophages.

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“…We put together four purified human macrophage datasets: (GSE35449, n = 21) (Beyer et al, 2012), (GSE85333, n = 185) (Regan et al, 2018), (GSE46903, n = 384) (Xue et al, 2014), (GSE55536, n = 33) (Zhang et al, 2015). GSE35449 (PBMC): CD14 + monocytes were isolated from Peripheral blood mononuclear cells (PBMC) using CD14-specific MACS beads and cultured in 6-well plates in media and provided various stimuli: IFN-γ, TNF-α, ultrapure LPS, IL-4, IL-13, or combinations thereof.…”

Section: Data Collection and Annotationmentioning

confidence: 99%

“…To validate TYROBP and FCER1G as universal biomarkers, we interrogated pure macrophage datasets collected from several human and mouse tissues (Figure 3). We combined four purified human macrophage datasets: (GSE35449, n = 21) (Beyer et al, 2012), (GSE85333, n = 185) (Regan et al, 2018), (GSE46903, n = 384) (Xue et al, 2014), (GSE55536, n = 33) (Zhang et al, 2015), and four diverse mouse macrophage datasets: (GSE82158, n = 163) (Misharin et al, 2017), (GSE38705, n = 511) (Orozco et al, 2012), (GSE62420, n = 56) (Grabert et al, 2016), and (GSE86397, n = 12) (Han et al, 2017).…”

Section: Fcer1g and Tyrobp Are Highly Expressed In Purified Macrophagmentioning

confidence: 99%

Computational Approach to Identifying Universal Macrophage Biomarkers

et al. 2020

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Macrophages engulf and digest microbes, cellular debris, and various diseaseassociated cells throughout the body. Understanding the dynamics of macrophage gene expression is crucial for studying human diseases. As both bulk RNAseq and single cell RNAseq datasets become more numerous and complex, identifying a universal and reliable marker of macrophage cell becomes paramount. Traditional approaches have relied upon tissue specific expression patterns. To identify universal biomarkers of macrophage, we used a previously published computational approach called BECC (Boolean Equivalent Correlated Clusters) that was originally used to identify conserved cell cycle genes. We performed BECC analysis using the known macrophage marker CD14 as a seed gene. The main idea behind BECC is that it uses massive database of public gene expression dataset to establish robust co-expression patterns identified using a combination of correlation, linear regression and Boolean equivalences. Our analysis identified and validated FCER1G and TYROBP as novel universal biomarkers for macrophages in human and mouse tissues.

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Effects of anti-inflammatory drugs on the expression of tryptophan-metabolism genes by human macrophages

Cited by 23 publications

References 70 publications

Propolis Exerts an Anti-Inflammatory Effect on PMA-Differentiated THP-1 Cells via Inhibition of Purine Nucleoside Phosphorylase

Propolis Exerts an Anti-Inflammatory Effect on PMA-Differentiated THP-1 Cells via Inhibition of Purine Nucleoside Phosphorylase

Computational approach to identifying universal macrophage biomarker

Computational Approach to Identifying Universal Macrophage Biomarkers

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