Serotonin (5-HT) Shapes the Macrophage Gene Profile through the 5-HT2B–Dependent Activation of the Aryl Hydrocarbon Receptor

Nieto, Concha; Rayo, Ignacio; Casas-Engel, Mateo de las; Izquierdo, Elena; Alonso, Bárbara; Béchade, Catherine; Maroteaux, Luc; Vega, Miguel A.; Corbí, Ángel L.

doi:10.4049/jimmunol.1901531

Cited by 32 publications

(20 citation statements)

References 113 publications

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“…This group also found that serotonin is increased significantly in hypertension compared to the control [ 28 ]. Serotonin receptors play a well-documented role in the pathogenesis of hypertension; therefore, it is not surprising that serotonin, a tryptophan metabolite, increases in hypertensive models [ 29 , 33 ]. Another study comparing plasma from pulmonary arterial hypertensive patients to a control group found that stearamide, a fatty acid, has decreased expression [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Common Metabolites in Two Different Hypertensive Mouse Models: A Serum and Urine Metabolome Study

et al. 2021

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Recent metabolomics studies have identified a wide array of microbial metabolites and metabolite pathways that are significantly altered in hypertension. However, whether these metabolites play an active role in pathogenesis of hypertension or are altered because of this has yet to be determined. In the current study, we hypothesized that metabolite changes common between hypertension models may unify hypertension’s pathophysiology with respect to metabolites. We utilized two common mouse models of experimental hypertension: L-arginine methyl ester hydrochloride (L-NAME)/high-salt-diet-induced hypertension (LSHTN) and angiotensin II induced hypertension (AHTN). To identify common metabolites that were altered across both models, we performed untargeted global metabolomics analysis in serum and urine and the resulting data were analyzed using MetaboAnalyst software and compared to control mice. A total of 41 serum metabolites were identified as being significantly altered in any hypertensive model compared to the controls. Of these compounds, 14 were commonly changed in both hypertensive groups, with 4 significantly increased and 10 significantly decreased. In the urine, six metabolites were significantly altered in any hypertensive group with respect to the control; however, none of them were common between the hypertensive groups. These findings demonstrate that a modest, but potentially important, number of serum metabolites are commonly altered between experimental hypertension models. Further studies of the newly identified metabolites from this untargeted metabolomics analysis may lead to a greater understanding of the association between gut dysbiosis and hypertension.

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Section: Discussionmentioning

confidence: 99%

Common Metabolites in Two Different Hypertensive Mouse Models: A Serum and Urine Metabolome Study

et al. 2021

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“…Global gene expression analysis was performed on RNA obtained from PBMC, monocytes, T lymphocytes, and B lymphocytes isolated immediately before or after IVIg therapy of four independent patients. RNA isolation, microarray analysis (whole human genome microarray, Agilent Technologies, Palo Alto, CA), and statistical treatment of microarray data were performed following previously described procedures [ 41 – 43 ]. Microarray data were deposited in the Gene Expression Omnibus ( http://www.ncbi.nlm.nih.gov/geo/ ) under accession nos.…”

Section: Methodsmentioning

confidence: 99%

Intravenous Immunoglobulins Promote an Expansion of Monocytic Myeloid-Derived Suppressor Cells (MDSC) in CVID Patients

et al. 2022

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Common variable immunodeficiency disorders (CVID), the most common primary immune deficiency, includes heterogeneous syndromes characterized by hypogammaglobulinemia and impaired antibody responses. CVID patients frequently suffer from recurrent infections and inflammatory conditions. Currently, immunoglobulin replacement therapy (IgRT) is the first-line treatment to prevent infections and aminorate immune alterations in CVID patients. Intravenous Immunoglobulin (IVIg), a preparation of highly purified poly-specific IgG, is used for treatment of immunodeficiencies as well as for autoimmune and inflammatory disorders, as IVIg exerts immunoregulatory and anti-inflammatory actions on innate and adaptive immune cells. To determine the mechanism of action of IVIg in CVID in vivo, we determined the effect of IVIg infusion on the transcriptome of peripheral blood mononuclear cells from CVID patients, and found that peripheral blood monocytes are primary targets of IVIg in vivo, and that IVIg triggers the acquisition of an anti-inflammatory gene profile in human monocytes. Moreover, IVIg altered the relative proportions of peripheral blood monocyte subsets and enhanced the proportion of CD14+ cells with a transcriptional, phenotypic, and functional profile that resembles that of monocytic myeloid-derived suppressor cells (MDSC). Therefore, our results indicate that CD14 + MDSC-like cells might contribute to the immunoregulatory effects of IVIg in CVID and other inflammatory disorders.

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“…In addition to underlying tissue hypoxemia, heart failure also has more tissue hypoxia. All these underlying pathologies shift metabolism to oxidative stress and perpetuate a chronic condition of inflammation with continuous production of IDO-1 and stimulation of the Tryptophan anti-inflammatory pathway with an increase in the Kynurenine/Tryptophan ratio leading to a state of tolerance due to KYN act on AhR receivers [13,30,31]. Furthermore, patients with insulin resistance have elevated serum 5-HT concentrations.…”

Section: Serotoninergic and Oxidative Signaturesmentioning

confidence: 99%

“…Another extra pathway in mammals can form NAD is the Sirtuins pathway, a family of mammalian NAD + dependent lysine histone deacetylases that are members of the highly conserved class III histone deacetylases and seven Sirtuingenes (Sirtuins 1-7). This pathway does not use Zn 2+ but uses NAD and nicotinamide adenine dinucleotide as cofactors in a family of mammalian NAD+ -dependent protein lysine histone deacetylases (SIRT3, SIRT4 and SIRT5) [21,[30][31][32][33][34][35][36][37][38][39][40][41][42].…”

Section: Dysmetabolism Oxidative Stress Uraemia and Wasting Syndrome ...mentioning

confidence: 99%

The COVID-19 "Bad Tryp" Syndrome: NAD/NADH+, Tryptophan Phenylalanine Metabolism and Thermogenesis like Hecatomb - The Hypothesis of Pathophysiology Based on a Compared COVID-19 and Yellow Fever Inflammatory Skeleton

D'Elia¹

2022

J Infect Dis Epidemiol

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Introduction:There is a significant imbalance in the generation of NAD/NADH+ (niacin), which affects chemical reactions in the intracellular environment in COVID-19 and yellow fever. From tryptophan and its metabolic pathways and oxidative stress, the process of understanding SARS-CoV-2 infection becomes more concrete, as the infection seems to interfere in these metabolic pathways, in addition to the paradoxical role of kynurenine that causes inflammation by blocking the BH4 pathway. Understanding metabolic changes in the elderly, people with type 2 diabetes (DM2), obese people or other chronic diseases with an inflammatory profile is to understand the severity of COVID-19 to improve clinical management.Hypothesis: SARS-CoV-2 may control the human immune response by acting on Furins and Cathepsins or triggering significant hypoxia; promotes the internalization of ACE-2, resulting in low absorption of some amino acids in the intestine, triggering immune suppression and metabolic syndrome (MS).Results: From overweight people to people with higher Body Mass Index (BMI) or insulin resistance, there is a tendency to hyperthermia by thermogenesis due to the consumption of serotonin (5-HT) and norepinephrine (NOR) in fat cells, triggering an increased inflammatory state and cell damage.It is typical of critically ill patients with COVID-19 who have been treated with antipyretic and antimicrobial drugs at elevated temperatures, but the correct treatment is an insulin pump. It is not fever; it is hyperthermia. The state of inflammation is related to the Kynurenine/BH4 imbalance.Objectives: This article aims to raise doubts to generate more discussions and bring more substrates to improve the patient's COVID-19. The primary pathophysiology of COVID-1 may be tryptophan syndrome due to kynurenine/ BH4 imbalance and the maintenance of the hypoxic environment that causes immunosuppression, tolerance and inflammation due to oxidative stress. A signature of innate immunity, oxidative stress, and tryptophan pathway imbalance.

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Serotonin (5-HT) Shapes the Macrophage Gene Profile through the 5-HT2B–Dependent Activation of the Aryl Hydrocarbon Receptor

Cited by 32 publications

References 113 publications

Common Metabolites in Two Different Hypertensive Mouse Models: A Serum and Urine Metabolome Study

Common Metabolites in Two Different Hypertensive Mouse Models: A Serum and Urine Metabolome Study

Intravenous Immunoglobulins Promote an Expansion of Monocytic Myeloid-Derived Suppressor Cells (MDSC) in CVID Patients

The COVID-19 "Bad Tryp" Syndrome: NAD/NADH+, Tryptophan Phenylalanine Metabolism and Thermogenesis like Hecatomb - The Hypothesis of Pathophysiology Based on a Compared COVID-19 and Yellow Fever Inflammatory Skeleton

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