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Article ; Conference proceedings: Neutrophil-Derived miRNA-223 Modulates Peritoneal Immunity in Patients with Cirrhosis During Spontaneous Bacterial Peritonitis

Frissen, Mick / Reißing, Johanna / Ibidapo-Obe, Oluwatomi / Trautwein, Christian / Bruns, Tony

2024 Volume 62, Issue 01

Event/congress	40. Jahrestagung der Deutschen Arbeitsgemeinschaft zum Studium der Leber, Haus der Technik e.V., Essen, 2024-01-26
Language	German
Publishing date	2024-01-01
Publisher	Georg Thieme Verlag
Publishing place	Stuttgart ; New York
Document type	Article ; Conference proceedings
ZDB-ID	201387-3
ISSN	1439-7803 ; 0044-2771 ; 0172-8504
ISSN (online)	1439-7803
ISSN	0044-2771 ; 0172-8504
DOI	10.1055/s-0043-1777658
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Zs.A 111: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.A 111/X: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)

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Article ; Conference proceedings: [No title information]

Ibidapo-Obe, Oluwatomi / Große, Karsten / Reißing, Johanna / Frissen, Mick / Trautwein, Christian / Bruns, Tony

Zeitschrift für Gastroenterologie

2023 Volume 61, Issue 01

Event/congress	39. Jahrestagung der Deutschen Arbeitsgemeinschaft zum Studium der Leber, Bochum, 2023-01-27
Language	German
Publishing date	2023-01-01
Publisher	Georg Thieme Verlag
Publishing place	Stuttgart ; New York
Document type	Article ; Conference proceedings
ZDB-ID	201387-3
ISSN	1439-7803 ; 0044-2771 ; 0172-8504
ISSN (online)	1439-7803
ISSN	0044-2771 ; 0172-8504
DOI	10.1055/s-0042-1759904
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Zs.A 111: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.A 111/X: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Immunomodulatory receptor VSIG4 is released during spontaneous bacterial peritonitis and predicts short-term mortality.

Reißing, Johanna / Lutz, Philipp / Frissen, Mick / Ibidapo-Obe, Oluwatomi / Reuken, Philipp A / Wirtz, Theresa H / Stengel, Sven / Quickert, Stefanie / Rooney, Michael / Große, Karsten / Zimmermann, Henning W / Trautwein, Christian / Stallmach, Andreas / Bruns, Tony

JHEP reports : innovation in hepatology

2021 Volume 4, Issue 1, Page(s) 100391

Abstract: Background & aims: V-set Ig-domain-containing 4 (VSIG4) is an immunomodulatory macrophage complement receptor modulating innate and adaptive immunity and affecting the resolution of bacterial infections. Given its expression on peritoneal macrophages ( ... ...

Abstract	Background & aims: V-set Ig-domain-containing 4 (VSIG4) is an immunomodulatory macrophage complement receptor modulating innate and adaptive immunity and affecting the resolution of bacterial infections. Given its expression on peritoneal macrophages (PMs), we hypothesised a prognostic role of peritoneal VSIG4 concentrations in patients with spontaneous bacterial peritonitis (SBP). Methods: We isolated PMs from patients with cirrhosis and analysed VSIG4 expression and release by flow cytometry, quantitative real-time PCR, ELISA, and confocal microscopy. We measured soluble VSIG4 concentrations in ascites from 120 patients with SBP and 40 patients without SBP and investigated the association of soluble VSIG4 in ascites with 90-day survival after SBP using Kaplan-Meier statistics, Cox regression, and competing-risks regression analysis. Results: VSIG4 expression was high on resting, large PMs, which co-expressed CD206, CD163, and tyrosine-protein kinase Mer (MERTK). Conclusions: VSIG4 is released from activated PMs into ascites during SBP. Higher peritoneal VSIG4 levels indicate patients with organ failure and poor prognosis. Lay summary: Patients with liver cirrhosis who develop ascites have an increased risk of infection and mortality. Our study shows that in patients with infected ascites, the complement receptor VSIG4 is released by resident macrophages into the abdominal fluid where it can be measured. Patients with elevated levels of this protein in ascites are at high risk of dying within 90 days.
Language	English
Publishing date	2021-11-03
Publishing country	Netherlands
Document type	Journal Article
ISSN	2589-5559
ISSN (online)	2589-5559
DOI	10.1016/j.jhepr.2021.100391
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Article ; Online: Bile Acids Activate NLRP3 Inflammasome, Promoting Murine Liver Inflammation or Fibrosis in a Cell Type-Specific Manner.

Holtmann, Theresa Maria / Inzaugarat, Maria Eugenia / Knorr, Jana / Geisler, Lukas / Schulz, Marten / Bieghs, Veerle / Frissen, Mick / Feldstein, Ariel E / Tacke, Frank / Trautwein, Christian / Wree, Alexander

Cells

2021 Volume 10, Issue 10

Abstract: Bile acids (BA) as important signaling molecules are considered crucial in development of cholestatic liver injury, but there is limited understanding on the involved cell types and signaling pathways. The aim of this study was to evaluate the ... ...

Abstract	Bile acids (BA) as important signaling molecules are considered crucial in development of cholestatic liver injury, but there is limited understanding on the involved cell types and signaling pathways. The aim of this study was to evaluate the inflammatory and fibrotic potential of key BA and the role of distinct liver cell subsets focusing on the NLRP3 inflammasome. C57BL/6 wild-type (WT) and
MeSH term(s)	Animals ; Bile Acids and Salts/immunology ; Cells, Cultured ; Hepatic Stellate Cells ; Hepatocytes ; Inflammasomes/immunology ; Inflammation/immunology ; Kupffer Cells ; Liver Diseases/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology ; Primary Cell Culture
Chemical Substances	Bile Acids and Salts ; Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; Nlrp3 protein, mouse
Language	English
Publishing date	2021-10-01
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10102618
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Article ; Online: Bidirectional Role of NLRP3 During Acute and Chronic Cholestatic Liver Injury.

Frissen, Mick / Liao, Lijun / Schneider, Kai Markus / Djudjaj, Sonja / Haybaeck, Johannes / Wree, Alexander / Rolle-Kampczyk, Ulrike / von Bergen, Martin / Latz, Eicke / Boor, Peter / Trautwein, Christian

Hepatology (Baltimore, Md.)

2021 Volume 73, Issue 5, Page(s) 1836–1854

Abstract: Background and aims: Cholestatic liver injury leads to cell death and subsequent inflammation and fibrosis. As shown for primary biliary cholangitis (PBC), the mechanisms and circuits between different cell death pathways leading to disease progression ... ...

Abstract	Background and aims: Cholestatic liver injury leads to cell death and subsequent inflammation and fibrosis. As shown for primary biliary cholangitis (PBC), the mechanisms and circuits between different cell death pathways leading to disease progression are incompletely defined. Common bile duct ligation (BDL) is a well-established murine model to mimic cholestatic liver injury. Here, we hypothesized that pyroptotic cell death by the Nucleotide-Binding Domain, Leucine-Rich-Containing Family, Pyrin Domain-Containing-3 (Nlrp3) inflammasome plays an essential role during human and murine cholestasis. Approach and results: NLRP3 activation was analyzed in humans with cholestatic liver injury. Wild-type (WT) and Nlrp3 Conclusions: NLRP3 activation correlates with disease activity in patients with PBC. NLRP3 has a differential role during acute and chronic cholestatic liver injury in contrast to kidney injury. Disease progression during chronic cholestasis can be targeted through small molecules and thus suggests a potential clinical benefit for humans, attenuating liver and kidney injury.
MeSH term(s)	Animals ; Apoptosis ; Cholestasis/metabolism ; Cholestasis/pathology ; Humans ; Inflammasomes/metabolism ; Liver/metabolism ; Liver/pathology ; Liver Failure, Acute/metabolism ; Liver Failure, Acute/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
Chemical Substances	Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; Nlrp3 protein, mouse
Language	English
Publishing date	2021-03-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1002/hep.31494
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Article ; Conference proceedings: The immunomodulatory receptor VSIG4 is released during spontaneous bacterial peritonitis and predicts short-term mortality

Reissing, Johanna / Lutz, Philipp / Frissen, Mick / Ibidapo-Obe, Oluwatomi / Reuken, PhilippA. / Wirtz, TheresaH. / Stengel, Sven / Quickert, Stefanie / Rooney, Michael / Große, Karsten / Zimmermann, HenningWolfgang / Trautwein, Christian / Stallmach, Andreas / Bruns, Tony

Zeitschrift für Gastroenterologie

2022 Volume 60, Issue 01

Event/congress	38. Jahrestagung der Deutsche Arbeitsgemeinschaft zum Studium der Leber, Mannheim, 2022-01-28
Language	English
Publishing date	2022-01-01
Publisher	Georg Thieme Verlag
Publishing place	Stuttgart ; New York
Document type	Article ; Conference proceedings
ZDB-ID	201387-3
ISSN	1439-7803 ; 0044-2771 ; 0172-8504
ISSN (online)	1439-7803
ISSN	0044-2771 ; 0172-8504
DOI	10.1055/s-0041-1740708
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Zs.A 111: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Gut microbiota depletion exacerbates cholestatic liver injury via loss of FXR signalling.

Schneider, Kai Markus / Candels, Lena Susanna / Hov, Johannes R / Myllys, Maiju / Hassan, Reham / Schneider, Carolin Victoria / Wahlström, Annika / Mohs, Antje / Zühlke, Sebastian / Liao, Lijun / Elfers, Carsten / Kilic, Konrad / Henricsson, Marcus / Molinaro, Antonio / Hatting, Maximilian / Zaza, Ayham / Drasdo, Dirk / Frissen, Mick / Devlin, A Sloan /

Gálvez, Eric J C / Strowig, Till / Karlsen, Tom H / Hengstler, Jan G / Marschall, Hanns-Ulrich / Ghallab, Ahmed / Trautwein, Christian

Nature metabolism

2021 Volume 3, Issue 9, Page(s) 1228–1241

Abstract: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology for which there are no approved therapeutic options. Patients with PSC display changes in gut microbiota and in bile acid (BA) composition; however, the ... ...

Abstract	Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology for which there are no approved therapeutic options. Patients with PSC display changes in gut microbiota and in bile acid (BA) composition; however, the contribution of these alterations to disease pathogenesis remains controversial. Here we identify a role for microbiota-dependent changes in BA synthesis that modulates PSC pathophysiology. In a genetic mouse model of PSC, we show that loss of microbiota-mediated negative feedback control of BA synthesis results in increased hepatic BA concentrations, disruption of bile duct barrier function and, consequently, fatal liver injury. We further show that these changes are dependent on decreased BA signalling to the farnesoid X receptor, which modulates the activity of the rate-limiting enzyme in BA synthesis, CYP7A1. Moreover, patients with advanced stages of PSC show suppressed BA synthesis as measured by serum C4 levels, which is associated with poor disease prognosis. Our preclinical data highlight the microbiota-dependent dynamics of BA metabolism in cholestatic liver disease, which could be important for future therapies targeting BA and gut microbiome interactions, and identify C4 as a potential biomarker to functionally stratify patients with PSC and predict disease outcomes.
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily B/genetics ; Animals ; Anti-Bacterial Agents/administration & dosage ; Bile Acids and Salts/metabolism ; Cholangitis, Sclerosing/metabolism ; Cholangitis, Sclerosing/pathology ; Cholestasis/metabolism ; Gastrointestinal Microbiome ; Humans ; Liver/metabolism ; Mice ; Prognosis ; Receptors, Cytoplasmic and Nuclear/metabolism ; Signal Transduction ; ATP-Binding Cassette Sub-Family B Member 4
Chemical Substances	ATP Binding Cassette Transporter, Subfamily B ; Anti-Bacterial Agents ; Bile Acids and Salts ; Receptors, Cytoplasmic and Nuclear ; farnesoid X-activated receptor (0C5V0MRU6P)
Language	English
Publishing date	2021-09-22
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2522-5812
ISSN (online)	2522-5812
DOI	10.1038/s42255-021-00452-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: The pro- and anticoagulant role of blood-borne phagocytes in patients with acute coronary syndrome.

Leers, Math P G / Keuren, Jeffrey F W / Frissen, Mick E P W / Huts, Mark / Kragten, Johannes A / Jie, Kon-Siong G

Thrombosis and haemostasis

2013 Volume 110, Issue 1, Page(s) 101–109

Abstract: This study was performed to gain further insight in pro- and anticoagulant characteristics of leukocytes in acute coronary syndrome (ACS). For this purpose, patients presenting on the emergency department (ED) with anginal chest pain were included in ... ...

Abstract	This study was performed to gain further insight in pro- and anticoagulant characteristics of leukocytes in acute coronary syndrome (ACS). For this purpose, patients presenting on the emergency department (ED) with anginal chest pain were included in this study. In peripheral blood, procoagulant tissue factor (TF) expression was measured in the different blood-borne phagocytes, i.e. neutrophilic granulocytes and the three different monocyte subsets based on expression of CD14 and CD16. Simultaneously, intracellular presence of platelet-(CD41) and/or endothelial cell-remnants (CD62e) was analysed in these different leukocyte subsets. Neutrophils showed a weak intracellular staining of CD62e and CD41 that increased with severity of ACS. Monocytes, and especially the classical (CD14++CD16-) and intermediate monocytes (CD14++CD16+) showed a clear and significant increase in intracellular CD41-staining after coronary damage. The different monocyte subsets showed an increase in expression of TF in severe ACS. Finally, it appeared that also neutrophils showed a significant increase in expression of TF on their membrane. In conclusion, this study showed an increased intracellular staining in blood-borne phagocytes for CD62e and CD41 in patients with ACS compared to non-cardiac related control patients. This indicates that at least in the acute phase of ACS phagocytosis of platelet and endothelial cell-remnants is increased. These data support the recent hypothesis that neutrophils protect against further thrombotic processes by clearing platelet and endothelial cell-remnants. In addition, this study shows that the different monocyte subsets are also involved in this process. Furthermore, both monocytes and neutrophils show increased TF expression in ACS.
MeSH term(s)	Acute Coronary Syndrome/blood ; Acute Coronary Syndrome/immunology ; Acute Disease ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD/metabolism ; Apoptosis ; Blood Cells/immunology ; Blood Cells/metabolism ; Blood Coagulation/immunology ; Cells, Cultured ; Endothelial Cells/metabolism ; Female ; Humans ; Male ; Middle Aged ; Phagocytes/immunology ; Phagocytosis/immunology ; Thromboplastin/metabolism ; Young Adult
Chemical Substances	Antigens, CD ; Thromboplastin (9035-58-9)
Language	English
Publishing date	2013-07
Publishing country	Germany
Document type	Journal Article
ZDB-ID	518294-3
ISSN	0340-6245
ISSN	0340-6245
DOI	10.1160/TH12-09-0643
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Uh III Zs.192: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Intestinal dysbiosis augments liver disease progression via NLRP3 in a murine model of primary sclerosing cholangitis.

Gut

2019 Volume 68, Issue 8, Page(s) 1477–1492

Abstract: Objective: There is a striking association between human cholestatic liver disease (CLD) and inflammatory bowel disease. However, the functional implications for intestinal microbiota and inflammasome-mediated innate immune response in CLD remain ... ...

Abstract	Objective: There is a striking association between human cholestatic liver disease (CLD) and inflammatory bowel disease. However, the functional implications for intestinal microbiota and inflammasome-mediated innate immune response in CLD remain elusive. Here we investigated the functional role of gut-liver crosstalk for CLD in the murine Mdr2 knockout Design: Male Results: Mdr2 Conclusions: MDR2-associated cholestasis triggers intestinal dysbiosis. In turn, translocation of endotoxin into the portal vein and subsequent NLRP3 inflammasome activation contribute to higher liver injury. This process does not essentially depend on caspase-8 in hepatocytes, but can be blocked by IDN-7314.
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily B/genetics ; Animals ; Bile Ducts ; Caspase 8/genetics ; Caspase Inhibitors/pharmacology ; Cholangitis, Sclerosing/metabolism ; Disease Progression ; Dysbiosis ; Gastrointestinal Microbiome/physiology ; Humans ; Immunity, Innate/drug effects ; Immunity, Innate/immunology ; Liver/immunology ; Mice ; Mice, Knockout ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology ; ATP-Binding Cassette Sub-Family B Member 4
Chemical Substances	ATP Binding Cassette Transporter, Subfamily B ; Caspase Inhibitors ; NLR Family, Pyrin Domain-Containing 3 Protein ; Nlrp3 protein, mouse ; Caspase 8 (EC 3.4.22.-)
Language	English
Publishing date	2019-03-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80128-8
ISSN	1468-3288 ; 0017-5749
ISSN (online)	1468-3288
ISSN	0017-5749
DOI	10.1136/gutjnl-2018-316670
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Article ; Online: CX3CR1 is a gatekeeper for intestinal barrier integrity in mice: Limiting steatohepatitis by maintaining intestinal homeostasis.

Schneider, Kai Markus / Bieghs, Veerle / Heymann, Felix / Hu, Wei / Dreymueller, Daniela / Liao, Lijun / Frissen, Mick / Ludwig, Andreas / Gassler, Nikolaus / Pabst, Oliver / Latz, Eicke / Sellge, Gernot / Penders, John / Tacke, Frank / Trautwein, Christian

Hepatology (Baltimore, Md.)

2015 Volume 62, Issue 5, Page(s) 1405–1416

Abstract: Unlabelled: Nonalcoholic fatty liver disease is seen as the hepatic manifestation of the metabolic syndrome and represents the most common liver disease in Western societies. The G protein-coupled chemokine receptor CX3CR1 plays a central role in ... ...

Abstract	Unlabelled: Nonalcoholic fatty liver disease is seen as the hepatic manifestation of the metabolic syndrome and represents the most common liver disease in Western societies. The G protein-coupled chemokine receptor CX3CR1 plays a central role in several metabolic syndrome-related disease manifestations and is involved in maintaining intestinal homeostasis. Because diet-induced intestinal dysbiosis is a driver for nonalcoholic fatty liver disease, we hypothesized that CX3CR1 may influence the development of steatohepatitis. In two independent models of diet-induced steatohepatitis (high-fat diet and methionine/choline-deficient diet), CX3CR1 protected mice from excessive hepatic steatosis and inflammation, as well as systemic glucose intolerance. Lack of Cx3cr1 expression was associated with significantly altered intestinal microbiota composition, which was linked to an impaired intestinal barrier. Concomitantly, endotoxin levels in portal serum and inflammatory macrophages in liver were increased in Cx3cr1-/- mice, indicating an increased inflammatory response. Depletion of intestinal microbiota by administration of broad-spectrum antibiotics suppressed the number of infiltrating macrophages and promoted macrophage polarization in liver. Consequently, antibiotic-treated mice demonstrated a marked improvement of steatohepatitis. Conclusion: Microbiota-mediated activation of the innate immune responses through CX3CR1 is crucial for controlling steatohepatitis progression, which recognizes CX3CR1 as an essential gatekeeper in this scenario.
MeSH term(s)	Animals ; Anti-Bacterial Agents/pharmacology ; Bacterial Translocation ; Blood Glucose/analysis ; CX3C Chemokine Receptor 1 ; Homeostasis ; Immunity, Innate ; Intestines/metabolism ; Intestines/microbiology ; Macrophages/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Microbiota ; Non-alcoholic Fatty Liver Disease/immunology ; Non-alcoholic Fatty Liver Disease/metabolism ; Receptors, Chemokine/physiology
Chemical Substances	Anti-Bacterial Agents ; Blood Glucose ; CX3C Chemokine Receptor 1 ; Cx3cr1 protein, mouse ; Receptors, Chemokine
Language	English
Publishing date	2015-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1002/hep.27982
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