Eleonora Distrutti

Eleonora Distrutti
Azienda Ospedaliera di Perugia · gastroenterologia

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173
Publications
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3308 Citations
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20172018201920202021202220230100200300400500600
20172018201920202021202220230100200300400500600
Introduction
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Publications

Publications (173)
Article
The composition of the bile acid pool is a function of the microbial metabolism of bile acids in the intestine. Perturbations of the microbiota shape the bile acid pool and modulate the activity of bile acid-activated receptors (BARs) even beyond the gastrointestinal tract, triggering various metabolic axes and altering host metabolism. Bile acids,...
Article
Full-text available
Liver disease is the second most common cause of mortality in HIV-infected persons. Exactly how HIV infection per se affects liver disease progression is unknown. Here we have investigated mRNA expression of 49 nuclear hormone receptors (NRs) and 35 transcriptional coregulators in HepG2 cells upon stimulation with the HIV matrix protein p17. This v...
Article
Introduction: Farnesoid-X-receptor (FXR) is the receptor for primary bile acids expressed in enterohepatic tissues where it regulates bile acid uptake, metabolism and disposal. For its role as a bile acid sensor, FXR has been thought to be an important target in the treatment of cholestatic disorders, a family of diseases in which endogenous bile...
Research
Full-text available
Bile acids (BAs) are experiencing a new life. Next to their ancestral roles in lipid digestion and solubilization, BAs are today recognized signaling molecules involved in many physiological functions. These signaling pathways involve the activation of metabolic nuclear receptors, mainly the BAs sensor FXR, and the dedicated membrane G-protein-coup...
Article
Full-text available
GPBAR1 is a bile acid activated receptor (BAR) for secondary bile acids, litocholic (LCA) and deoxycholic acid (DCA), expressed in the entero-hepatic tissues and in the vasculature by endothelial and smooth muscle cells. Despite bile acids cause vasodilation, it is unclear why these effects involve GPBAR1 and the vascular phenotype of GPBAR1 defici...
Article
Full-text available
Bile acids are the end product of cholesterol metabolism. Synthesized in the liver, primary bile acids are secreted by hepatocytes and are transformed by intestinal microbiota into secondary bile acids. In addition to their role in cholesterol and lipid absorption, bile acids act as signaling molecules activating a family of nuclear and G-protein-c...
Article
Introduction: Bile acids, the end product of cholesterol metabolism, are signaling molecules. The farnesoid X receptor (FXR) is a bile acid sensor and is part of a network of nuclear receptors that regulate bile acid homeostasis. In addition to FXR, bile acids activate other nuclear receptors (CAR, PXR and VDR), cell surface receptors including th...
Article
Full-text available
The intestinal microbiota is increasingly recognized as a complex signaling network that impacts on many systems beyond the enteric system modulating, among others, cognitive functions including learning, memory and decision-making processes. This has led to the concept of a microbiota-driven gut-brain axis, reflecting a bidirectional interaction b...
Article
Full-text available
In the present study we provide evidence that solomonsterol A, a selective pregnane X receptor (PXR) agonist isolated from the marine sponge Theonella swinhoei, exerts anti-inflammatory activity and attenuates systemic inflammation and immune dysfunction in a mouse model of rheumatoid arthritis. Solomonsterol A was effective in protecting against t...
Article
The protease inhibitor ritonavir is part of the highly active anti-retroviral therapy (HAART) successfully used in the treatment of human immunodeficiency virus (HIV)-1 infection. There is evidence that ritonavir alters intestinal permeability and induces damage to the small intestine. Because HIV infected patients taking HAART are at high risk for...
Article
Glucocorticoids (GCs) are important endocrine regulators of a wide range of physiological processes ranging from immune function to glucose and lipid metabolism. For decades, synthetic glucocorticoids such as dexamethasone have been the cornerstone for the clinical treatment of inflammatory bowel diseases (IBD). A previous study have shown that far...
Article
Full-text available
The Farnesoid-X-receptor (FXR) and the Liver-x-receptors (LXRs) are bile acids activated receptors highly expressed in the eneterohepatic tissues. The mechanisms that support the beneficial effects of bariatric surgery are only partially defined. Here we have investigated the effects of ileal interposition (IT), a surgical relocation of distal ileu...
Article
Full-text available
Irritable bowel syndrome (IBS) is linked to post-inflammatory and stress-correlated factors that cause changes in the perception of visceral events. Probiotic bacteria may be effective in treating IBS symptoms. Here, we have investigated whether early life administration of VSL#3, a mixture of 8 probiotic bacteria strains, protects against developm...
Article
Full-text available
Background Toll like receptors (TLRs) sense the intestinal microbiota and regulate the innate immune response. A dysregulation of TLRs function participates into intestinal inflammation. Farnesoid X Receptor (FXR) is a nuclear receptor and bile acid sensor highly expressed in entero-hepatic tissues. FXR regulates lipid metabolism and innate immunit...
Article
Low doses of aspirin (acetylsalicylic acid; ASA) and non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of gastrointestinal bleeding. GPBAR1 is a bile acid receptor expressed in the gastrointestinal tract. Here, we have investigated whether GPBAR1 was required for mucosal protection in models of gastrointestinal injury caused by ASA a...
Article
Nuclear receptors (NRs) are a large family of evolutionarily conserved and ligand-regulated transcription factors. The farnesoid X receptor (FXR) and the pregnane X receptor (PXR) are two bile-acid-activated receptors highly expressed in enterohepatic tissues essential for bile acids and xenobiotic metabolism. More than 1600 new steroidal structure...
Article
Full-text available
This article is a report on a symposium sponsored by the American Society for Pharmacology and Experimental Therapeutics and held at the Experimental Biology 12 meeting in San Diego, CA. The presentations discussed the roles of a number of nuclear receptors in regulating glucose and lipid homeostasis, the pathophysiology of obesity-related disease...
Article
Full-text available
Signals generated by the inflammed intestine are thought to contribute to metabolic derangement. The intestinal microbiota contributes to instructing the immune system beyond the intestinal wall and its modulation is a potential target for treating systemic disorders. To investigate the pathogenetic role of low grade intestinal inflammation in the...
Article
The farnesoid X receptor (FXR) is a bile sensor that acts in coordination with other nuclear receptors to regulate essential steps in bile acid uptake, metabolism and excretion. In addition, FXR is an ancillary receptor involved in lipid and glucose homeostasis. Steroidal and non-steroidal FXR ligands are currently available. Both groups have shown...
Article
The glucocorticoid receptor (GR) is a master gene orchestrating the activation of gluconeogenic genes in the liver in response to food withdrawal. Mechanisms of GR regulation by other nuclear receptors, however, are poorly defined. Here, we report that the farnesoid X receptor (FXR), a bile acid sensor, activates gluconeogenic pathways in the liver...
Article
Invasion and metastasis are critical determinants of gastrointestinal and liver cancers morbidity. Genes and molecules participating in these steps (e.g. growth factors and their receptors, cell cycle regulators, cell adhesion molecules, matrix degrading enzymes) have been progressively clarified. Activated Wnt signaling pathway has been found in t...
Article
The farnesoid-x-receptor (FXR), the constitute-androstane-receptor (CAR) and the pregnane-x-receptor (PXR) are ligand regulated nuclear receptors highly expressed in the liver and intestine supervising essential steps in the metabolism of xeno and endo-biotics in entero-hepatic tissues. Primary and secondary bile acids function as receptor agonists...
Data
Results of docking calculation of interaction of ciprofloxacin and TLCA with GP-BAR1 binding site. (DOC)
Article
Full-text available
GP-BAR1, a member G protein coupled receptor superfamily, is a cell surface bile acid-activated receptor highly expressed in the ileum and colon. In monocytes, ligation of GP-BAR1 by secondary bile acids results in a cAMP-dependent attenuation of cytokine generation. To investigate the role GP-BAR1 in regulating intestinal homeostasis and inflammat...
Article
Background and aims: Obesity-driven lipotoxicity is a risk factors for cardiovascular disease. The Farnesoid X Receptor (FXR) is a bile acids sensor and member of the nuclear receptor superfamily. Activation of FXR lowers plasma triacylglycerols and glucose levels through a mechanism that involves both the repression of key regulatory genes in the...
Article
Inflammation-driven immune dysfunction supports the development of several chronic human disorders including inflammatory bowel diseases and rheumatoid arthritis. Macrolides are effective antibiotics endowed with immunomodulatory effects. In this study we report the chemical synthesis and the pharmacological characterization of CSY0073, a non-antib...
Article
Traditional nonsteroidal anti-inflammatory drugs, tNSAIDs, are effective medication for prevention of ischemic events and treatment of pain, fever and inflammation. However their use associates with a significant risk to develop gastrointestinal and cardiovascular complications. Low doses of acetyl salicylic acid (ASA) and effective doses of tNSAID...
Article
Full-text available
Adipocytes from mesenteric white adipose tissue amplify the inflammatory response and participate in inflammation-driven immune dysfunction in Crohn's disease by releasing proinflammatory mediators. Peroxisome proliferator-activated receptors (PPAR)-α and -γ, pregnane x receptor (PXR), farnesoid x receptor (FXR) and liver x-receptor (LXR) are ligan...
Article
A dysregulated interaction between intestinal epithelial cells (IEC) and components of innate immunity is a hallmark of inflammatory bowel diseases. Rifaximin is a poorly absorbed oral antimicrobial agent increasingly used in the treatment of inflammatory bowel diseases that has been demonstrated to act as a gut-specific ligand for the human nuclea...
Article
Hepatic transport and metabolism of glutamate and glutamine are regulated by intervention of several proteins. Glutamine is taken up by periportal hepatocytes and is the major source of ammonia for urea synthesis and glutamate for N-acetylglutamate (NAG) synthesis, which is catalyzed by the N-acetylglutamate synthase (NAGS). Glutamate is taken up b...
Article
The regulation of hepatic stellate cells (HSCs) by bacterial lipopolysaccharide (LPS) represents a recently-discovered and novel mechanism for hepatic injury and fibrosis. Stimulation of HSCs with LPS results in a rapid and marked induction of interleukin (IL)1β, IL6 and tumor necrosis factor α. These events lead to the development of the activated...
Article
Low doses of acetyl salicylic acid (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal damage. The farnesoid X receptor (FXR) is a bile acid sensor essential for maintenance of intestinal homeostasis. Here, we have investigated whether FXR is required for mucosal protection in models of gastrointestinal injury caused by...
Article
Physiopathological mechanisms and treatment of pain remain a significant challenge. In the last decade, the gasotransmitter hydrogen sulphide (H(2)S) has received wide attention for its ability to act as a multilevel regulatory molecule in a variety of biologic functions in mammals including modulation of pain processing. Results from preclinical m...
Article
Multidrug resistance protein-4 (MRP4) is a member of the multidrug resistance associated gene family that is expressed on the basolateral membrane of hepatocytes and undergoes adaptive up-regulation in response to cholestatic injury or bile acid feeding. In this study we demonstrate that farnesoid X receptor (FXR) regulates MRP4 in vivo and in vitr...
Article
The pregnane-X-receptor (PXR) is master gene overseeing detoxification of wide number of xenobiotics and is critical for maintenance of intestinal integrity. The intestinal expression of genes involved in cellular detoxification is down-regulated in patients with inflammatory bowel diseases (IBD). Rifaximin is a non-absorbable antibiotic endowed wi...
Data
LPMC were isolated from freshly obtained colonic specimens. After excision of all visible lymphoid follicles, colons were digested with type IV collagenase (Sigma) for 20 min in a shaking incubator at 37°C; this step was repeated twice. The released cells were then layered on a 40%-100% Percoll gradient (Pharmacia, Upsala, Sweden) and spun at 1,800...
Data
Total lysates from colon were prepared by E1A-buffer. Protein levels in tissue extract were quantified with Bradford reagent. Proteins, 30 µgrams, (a pool of 5 different animals, 6 µgrams each) were separated by polyacrylamide gel electrophoresis, transferred to nitrocellulose membranes (Bio-Rad, Hercules, CA) and than probed with primary anti-FXR...
Data
Nubiscan analysis (http://www.nubiscan.unibas.ch) of the mouse CD36 promoter region revealed one potential SREBP1 binding site, TTCACACCAG, located at −1562 bp from the transcriptional starting site ATG. To assess the functionality of this SRE (Sterol Regulatory Element) we carried a ChIP experiment with an anti SREBP1 antibody (see Materials and M...
Data
In silico studies and GP-BAR1 homology modeling. (DOC)
Article
Full-text available
Although human immunodeficiency virus (HIV)-related morbidity and mortality rates in patients treated with a combination of high active antiretroviral therapy (HAART) have declined, significant metabolic/vascular adverse effects associated with the long term use of HIV protease inhibitors (PIs) have emerged as a significant side effect. Here we ill...
Article
In addition to their role in dietary lipid absorption bile acids are signaling modules activating nuclear receptors and at least one G-protein coupled receptor named the TGR5. With a different rank of potency primary and secondary bile acids activate a subset of nuclear receptors including the farnesoid-X-receptor (FXR, NR1H4); the constitutive and...
Article
In addition to their role in dietary lipid absorption bile acids are signaling modules activating nuclear receptors and at least one G-protein coupled receptors named the TGR5. With a different rank of potency primary and secondary bile acids activates a subset of nuclear receptors including the farnesoid-X-receptor (FXR, NR1H4); the constitutive a...
Article
Full-text available
Hydrogen sulphide (H2S) is a gaseous neuro-mediator that exerts analgesic effects in rodent models of visceral pain by activating KATP channels. A body of evidence support the notion that KATP channels interact with endogenous opioids. Whether H2S-induced analgesia involves opioid receptors is unknown. The perception of painful sensation induced by...
Data
Animals. This file describes the animals used.
Data
Effect of H2S on MOR. This file describes the methods used to determine MOR activation
Data
Effects of KATP channels. This file describes the method used for blocking the KATP channels.
Data
Spinal cFOS expression. This file describes the method used for determining spinal cFos expression.
Data
CRD and behavioral testing. This file describes the behavioral testing used in the in vivo studies.
Data
Effects of the opioid receptors antagonism. This file describes the methods used for blocking the opioid receptors.
Data
Effect of H2S on MOR internalization. This file describes the methods used to detect MOR internalization.
Data
Effect of H2S on AKT phosphorylation. This file describes the methods used to determine AKT phosphorylation.
Data
Effects of glibenclamide. This file describes the methods used to determine the effects of KATP channels blockade.
Article
The farnesoid X receptor (FXRα) is a metabolic nuclear receptor and bile acid sensor expressed in the liver and intestine. Physiological studies have shown that FXR.. exerts regulatory roles in bile acids, lipid and glucose homeostasis. FXR ligands of steroidal and non-steroidal structure have been described. Both ligand groups have shown limitatio...
Article
Full-text available
The farnesoid X receptor (FXR) is a bile acid-regulated nuclear receptor expressed in enterohepatic tissues. In this study we investigated whether FXR is expressed by cells of innate immunity and regulates inflammation in animal models of colitis. Acute (7 days) and chronic (8 wk) colitis were induced in wild-type and FXR(-/-) mice by intrarectal a...
Article
Full-text available
Immune-mediated liver diseases including autoimmune and viral hepatitis are a major health problem worldwide. In this study, we report that activation of the farnesoid X receptor (FXR), a member of the ligand-activated nuclear receptor superfamily and bile sensor highly expressed in the liver, attenuates liver injury in a model of autoimmune hepati...