P31 Prof. Dr. Wree/Prof. Dr. Trautwein
Inflammasome activation during cholestatic liver injury: A trigger of fibrosis progression

We hypothesize that toxic bile acids or cholestasis trigger NLRP3 inflammasome activation, thereby driving cholestatic liver fibrosis. In collaboration with the other inflammasome-focused projects, we plan to identify cell-specific inflammasome components involved in immune-mediated liver injury and study their interaction with hepatic stellate cells. We will analyze bile acid alterations, test the validity of inflammasome components as biomarkers in patients with cholestatic liver disease and apply novel inflammasome inhibitors to stop disease progression. [...]

Publications

• Krause J. , Grabsch H. I., Kloor M., Jendrusch M., Echle A., Buelow R. D., Boor P., Luedde T., Brinker T. J., Trautwein C., Pearson A. T., Quirke P., Jenniskens J., Offermans K., van den Brandt P. A., Kather J. N. (2021): Deep learning detects genetic alterations in cancer histology generated by adversarial networks. Journal of Pathology, 254(1), 70-79, [5.979]
• Kuscuoglu D. , Bewersdorf L., Wenzel K., Gross A., Kobazi Ensari G., Luo Y., Kilic K., Hittatiya K., Golob-Schwarzl N., Leube R. W., Preisinger C., George J., Metwally M., Eslam M., Lampertico P., Petta S., Mangia A., Berg T., Boonstra A., Brouwer W. P., Abate M. L., Loglio A., Sutton A., Nahon P., Schaefer B., Zoller H., Aigner E., Trautwein C., Haybaeck J., Strnad P. (2021): Dual proteotoxic stress accelerates liver injury via activation of p62-Nrf2. Journal of Pathology, 254(1), 80-91, [5.979]
• Fromme M. , Schneider C. V., Pereira V., Hamesch K., Pons M., Reichert M. C., Benini F., Ellis P., Thorhauge K. T., Mandorfer M., Burbaum B., Woditsch V., Chorostowska-Wynimko J., Verbeek J., Nevens F., Genesca J., Miravitlles M., Nuñez A., Schaefer B., Zoller H., Janciauskiene S., Abreu N., Jasmins L., Gaspar R., Liberal R., Macedo G., Mahadeva R., Gomes C., Schneider K. M., Trauner M., Krag A., Gooptu B., Thorburn D., Marshall A., Hurst J. R., Lomas D. A., Lammert F., Gaisa N. T., Clark V., Griffiths W., Trautwein C., Turner A. M., McElvaney N. G., Strnad P. (2021): Hepatobiliary phenotypes of adults with alpha-1 antitrypsin deficiency. GUT 2021, gutjnl-2020-323729, [19.819]
• Heinrichs D. , Brandt E. F., Fischer P., Köhncke J., Wirtz T. H., Guldiken N., Djudjaj S., Boor P., Kroy D., Weiskirchen R., Bucala R., Wasmuth H. E., Strnad P., Trautwein C., Bernhagen J., Berres M.-L. (2021): Unexpected Pro-Fibrotic Effect of MIF in Non-Alcoholic Steatohepatitis Is Linked to a Shift in NKT Cell Populations. Cells, in press, [5.656]
• Wirtz T. H. , Reuken P. A., Jansen C., Fischer P., Bergmann I., Backhaus C., Emontzpohl C., Reißing J., Brandt E. F., Koenen T. M., Schneider K. M., Schierwagen R., Brol M. J., Chang J., Zimmermann H. W., Köse-Vogel N., Eggermann T., Kurth I., Stoppe C., Bucala R., Bernhagen J., Praktiknjo M., Stallmach A., Trautwein C., Trebicka J., Bruns T., Berres M.-L. (2021): Balance between macrophage migration inhibitory factor and sCD74 predicts outcome in patients with acute decompensation of cirrhosis. JHEP Reports, in press,
• Paffenholz P. (2020): Perception of the 2020 SARS-CoV-2 pandemic among medical professionals in Germany: results from a nationwide online survey. Emerging Microbes & Infectons, 9(1), 1590-1599,
• Cubero F. J. , Mohamed M. R., Woitok M. M., Zhao G., Hatting M., Nevzorova Y. A., Chen C., Haybaeck J., de Bruin A., Avila M. A., Boekschoten m. V., Davis R. J., Trautwein C. (2020): Loss of JNK1/2 function in liver epithelial cells triggers biliary hyperprolif eration resembling cholangiocarcinoma. Hepatol Commun., 4(6), 834-851, [0.800]
• Woitok M. M. , Zoubek M. E., Doleschel Dr., Bartneck M., Mohamed M. R., Kießling F., Lederle W., Trautwein C., Cubero F. J. (2020): Lipid-encapsulated siRNA for hepatocyte-directed treatment of advanced liver disease. Cell Death Dis, 11(5), 343,
• Drescher H. K. , Schippers A., Rosenhain S., Gremse F., Bongiovanni L., de Bruin A., Eswaran S., Gallage S. U., Pfister D., Szydlowska M., Heikenwalder M., Weiskirchen S., Wagner N., Trautwein C., Weiskirchen R., Kroy D. C. (2020): L-Selectin/CD62L is a Key Driver of non-alcoholic Steatohepatitis in Mouse and Men. Cells, 9(5), 1106, [5.656]
• Hübbers A. , Hennings J., Lambertz D., Haas U., Trautwein C., Nevzorova Y. A., Sonntag R., Liedtke C. (2020): Pharmacological Inhibition of Cyclin dependent Kinases Triggers Anti-Fibrotic Effects in Hepatic stellate cells in vitro. International Journal of Molecular Science, 21(9), 3267, [4.183]
• Schneider K. M. , Elfers C., Ghallab A., Schneider C. V., Galvez E. J. C., Mohs A., Gui W., Candels L. S., Wirtz T. H., Zuehlke S., Spiteller M., Myllys M., Roulet A., Ouzerdine A., Lelouvier B., Kilic K., Liao L., Nier A., Latz E., Bergheim I., Thaiss C. A., Hengstler J. G., Strowig T., Trautwein C. (2020): Intestinal dysbiosis amplifies acetaminophen induced acute liver injury. Cell Mol Gastroenterol Hepatol, S2352-345X(20), 30181-8, [6.850]
• Schneider C.V. , Hamesch K., Gross A., Mandorfer M., Moeller L. S., Pereira V., Pons M., Kuca P., Reichert M. C., Benini F., Burbaum B., Voss J., Gutberlet M., Woditsch V., Lindhauer C., Fromme M., Kümpers J., Bewersdorf L., Schaefer B., Eslam M., Bals R., Janciauskiene S., Carvão J., Neureiter D., Zhou B., Wöran K., Bantel H., Geier A., Dirrichs T., Stickel F., Teumer A., Verbeek J., Nevens F., Govaere O., Krawczyk M., Roskams T., Haybaeck J., Lurje G., Chorostowska-Wynimko J., Genesca J., Reiberger T., Lammert F., Krag A., George J., Anstee Q. M., Trauner M., Datz C., Gaisa N. T., Denk H., Trautwein C., Aigner E., Strnad P. (2020): Liver Phenotypes of European Adults Heterozygous or Homozygous for Pi∗Z Variant of AAT (Pi∗MZ vs Pi∗ZZ genotype) and Noncarriers. Gastroenterology, 159, 534-548,
• Echle A. , Grabsch H. I., Quirke P., van den Brandt P. A., West N. P., Hutchins G. G. A., Heij L. R., Tan X., Richman S. D., Krause J., Alwers E., Jenniskens J., Offermans K., Gray R., Brenner H., Chang-Claude J., Trautwein C., Pearson A. T., Boor P., Luedde T., Gaisa N. T., Hoffmeister M., Kather J. N. (2020): Clinical-Grade Detection of Microsatellite Instability in Colorectal Tumors by Deep Learning. Gastroenterology, 159, 1406-1416,
• Wirtz T. H. , Fischer P., Backhaus C., Bergmann I., Brandt E. F., Heinrichs D., Koenen M. T., Schneider K. M., Eggermann T., Kurth I., Stoppe C., Bernhagen J., Bruns T., Fischer J., Berg T., Trautwein C., Berres M.-L. 1 (2019): Genetic Variants in the Promoter Region of the Macrophage Migration Inhibitory Factor are Associated with the Severity of Hepatitis C Virus-Induced Liver Fibrosis. Internation Journal of Molecular Sciences, 20(15), 3753, [3.687]
• Zoubek M. E. , Woitok M. M., Sydor S., Nelson L. J., Bechmann L. P., Lucena M. I., Andrade R. J.,Bast A., Koek G.H., Trautwein C., Cubero F. J. (2019): Protective role of c‐Jun N‐terminal kinase‐2 (JNK2) in ibuprofen‐induced acute liver injury. Journal of Pathology, 247, 110-122, [6.253]
• Tacke F. , Spehlmann M.E., Vucur M., Benz F., Luedde M., Cardenas D.V., Roy S., Loosen S, Hippe H.J., Frey N., Trautwein C., Koch A., Roderburg C., Luedde T. (2019): miR-155 predicts lpongterm mortality in critically ill patiens younger than 65 years. Mediators Inflamm, [3.549]
• Spivak I. , Arora J., Meinzer C., Durkalski-Mauldin V., Lee W. M., Trautwein C., Fontana R. J., Strnad P. (2019): Low Serum Hepicidin is associated with reuced short-term survival in adults with acute liver failure. Hepatology, 59(5), 2136-2149, [14.079]
• Schneider K. M. , Mohs A., Kilic K., Candels L. S., Elfers C., Bennek E., Schneider L. B., Heymann F., Gassler N., Penders J., Trautwein C. (2019): Intestinal Microbiota Protects against MCD Diet-Induced Steatohepatitis. International Journal of Molecular Sciences, 20(2), 308, [4.183]
• Mohs A. , Kuttkat N., Otto T., Youssef S. A., De Bruin A., Trautwein C. (2019): MyD88-dependent signaling in non-parenchymal cells promotes liver carcinogenesis. Carcinogenesis, [4.004]
• Loosen S. H. , Tacke F., Püthe N., Binneboesel M., Wiltberger G., Alizai P. H., Kather J. N., Paffenholz P., Ritz T., Koch A., Bergmann F., Trautwein C., Longerich T., Roderburg C., Neumann U. P., Luedde T. (2019): High baseline soluble urokinase plasminogen activator receptor (suPAR) serum levels indicate adverse outcome after resection of pancreatic adenocarcinoma. Carcinogenesis, 40(8), 947–955, [4.004]
• Liao L. , Schneider K. M., Galvez E. J. C., Frissen M., Marschall H.-U., Su H., Hatting M., Wahlström A., Haybaeck J., Puchas P., Mohs A., Peng J., Bergheim I., Nier A., Hennings J., Reißing J., Zimmermann H. W., Longerich T., Strowig T., Liedtke, C., Cubero F. J., Trautwein C. (2019): Intestinal dysbiosis augments liver disease progression via NLRP3 in a murine model of primary sclerosring cholangitis. Gut, 68, 1477-1492, [17.160]
• Hohlstein P. , Gussen H., Bartneck M., Warzecha K. T., Roderburg C., Buendgens L., Trautwein C., Koch A., Tacke F. (2019): Prognostic Relevance of Altered Lymphocyte Subpopulations in Critical Illness and Sepsis. Journal of Clinical Medicine, [5.688]
• Hansel C. , Erschfeld S., Baues M., Lammers T., Weiskirchen R., Trautwein C., Kroy D.C., Drescher H.K. (2019): The inhibitory T cell receptors PD1 and 2B4 are differentially regulated on CD4 and CD8 T cells in a mouse model of non-alcoholic steatohepatitis. Front Pharmacol, 10, 244, [3.845]
• Hansel C. , Erschfeld S., Baues M., Lammers T., Weiskirchen R., Trautwein C., Kroy D. C., Drescher H. K. (2019): The Inhibitory T Cell Receptors PD1 and 2B4 Are Differentially Regulated on CD4 and CD8 T Cells in a Mouse Model of Non-alcoholic Steatohepatitis. frontiers in Pharmacology, [3.845]
• Dutton Sackett S. , Otto T., Mohs A., Sander L. E., Strauch S., Streetz K.L., Kroy D. C., Trautwein C. (2019): Myeloid cells require gp130 signaling for protective anti-inflammatory functions during sepsis. The FASEB Journal, 33(5), [5.498]
• Drescher H. K. , Weiskirchen R., Fülöp A., Hopf C., Gonzáles de San Roman E., Huesgen P.F., de Bruin A., Christ A., Tolba R., Trautwein C., Kroy D.C. (2019): The influence of different fat sources on steatohepatitis and fibrosis development in the Western diet mouse model of non-alcoholic steatohepatitis (NASH). Front Physiol, 10, 770, [3.394]
• Cubero F. J. , Woitok M. M., Zoubek M. E., de Bruin A., Hatting M., Trautwein C. (2019): Disruption of the FasL/FasR axis protects against inflammation-derived tumorigenesis in chronic liver disease. Cell Death & Disease, 10, 115, [5.959]
• Cubero F. J. , Peng J., Liao L., Su H., Zhao G., Zoubek M. E., Macías-Rodríguez R., Ruiz-Margain A., Reißing J., Zimmermann H. W., Gassler N., Luedde T., Liedtke C., Hatting M., Trautwein C. (2019): Inactivation of caspase 8 in liver parenchymal cells confers protection against murine obstructive cholestasis. Journal of Hepatology, 69(6), 1326-1334, [10.590]
• Yagmur E. , Buendgens L., Herbers U., Beeretz A., Weiskirchen R., Koek G. H., Trautwein C., Tacke F., Koch A. (2018): High mobility group box 1 as a biomarker in critically ill patients. J Clin Lab Anal, 32(8), e22584, [1.728]
• Warzecha K. T. , Bartneck M., Möckel D., Appold L., Ergen C., Al Rawashdeh W., Gremse F., Niemietz P. M., Jahnen‐Dechent W., Trautwein C., Kiessling F., Lammers T., Tacke F. (2018): Targeting and Modulation of Liver Myeloid Immune Cells by Hard-Shell Microbubbles. Adv Biosyst, 2(5), 1-24, [2.855]
• Vucur M. , Roderburg C., Kaiser L., Schneider A. T., Roy S., Loosen S. H., Luedde M., Trautwein C., Koch A., Tacke F., Luedde T. (2018): Elevated Serum Levels of Mixed Lineage Kinase Domain-Like Protein Predict Survival of Patients during Intensive Care Unit Treatment. Dis Markers, , 1983421, [2.761]
• Sonntag R. , Giebeler N., Nevzorova Y. A., Bangen J. M., Fahrenkamp D., Lambertz D., Haas U., Hu W., Gassler N., Cubero F. J., Müller-Newen G., Abdallah A. T., Weiskirchen R., Ticconi F., Costa I. G., Barbacid M., Trautwein C., Liedtke C. (2018): Cyclin E1 and Cyclin-dependent kinase 2 are critical for initiation, but not for progression of hepatocellular carcinoma. Proc Natl Acad Sci USA, 115, 9282-9287, [9.580]
• Pombeiro I. , Loosen S. H, Roy S., Schueller F., Niewenhuisen L., Luedde M., Vucur M., Tacke F., Binnebösel M., Schoening W., Trautwein C., Luedde T., Neumann U. P., Roderburg C. (2018): Differential Roles of Tumor Necrosis Factor Ligand Superfamily Members as Biomarkers in Pancreatic Cancer. J Clin Med, 7(7), 175, [5.583]
• Luedde M. , Spehlmann M. E., Hippe H.-J., Loosen S. H., Roy S., Cardenas D. V., Vucur M., Frey N., Koch A., Luedde T., Trautwein C., Tacke F., Roderburg C. (2018): Serum levels of kisspeptin are elevated in critically ill patients. PLoS ONE, 13(10), e0206064, [2.776]
• Loosen S. H. , Tacke F., Binnebosel M., Leyh C., Vucur M., Heitkamp F., Schoening W., Ulmer T. F., Alizai P. H., Trautwein C., Koch A., Longerich T., Roderburg C., Neumann U. P., Luedde T. (2018): Serum levels of soluble urokinase plasminogen activator receptor (suPAR) predict outcome after resection of colorectal liver metastases. Oncotarget, 9(43), 27027-27038, [5.168]
• Loosen S. H. , Schulze-Hagen M., Leyh C., Benz F., Vucur M., Kuhl C., Trautwein C., Tacke F., Bruners P., Roderburg C., Luedde T. (2018): IL-6 and IL-8 Serum Levels Predict Tumor Response and Overall Survival after TACE for Primary and Secondary Hepatic Malignancies. Int J Mol Sci, 19(6), 1766, [4.183]
• Levada K. , Guldiken N., Zhang X., Vella G., Mo F., James L. P., Haybaeck J., Kessler S. M., Kiemer A. K., Ott T., Hartmann D., Hüser N., Ziol M., Trautwein C., Strnad P. (2018): Hsp72 protects from liver injury via attenuation of hepatocellular death, oxidative stress and JNK-signaling. J Hepatol, 68, 996-1005, [18.946]
• Lehmann J. M. , Claus K., Jansen C., Pohlmann A., Schierwagen R., Meyer C., Thomas D., Manekeller S., Claria J., Strassburg C. P., Trautwein C., Wasmuth H. E., Berres M. L., Trebicka J. (2018): Circulating CXCL10 in cirrhotic portal hypertension might reflect systemic inflammation and predict ACLF and mortality. Liver Int, 38(5), 875-884, [5.542]
• Koch A. , Yagmur E., Linka J., Schumacher F., Bruensing J., Buendgens L., Herbers U., Koek G. H., Weiskirchen R., Trautwein C., Tacke F. (2018): High Circulating Caspase-Cleaved Keratin 18 Fragments (M30) Indicate Short-Term Mortality in Critically Ill Patients. Dis Markers, 8583121, [2.761]
• Koch, A. , Yagmur, E., Hoss, A., Buendgens, L., Herbers, U., Weiskirchen, R., Koek, G. H., Trautwein, C., Tacke, F. (2018): Clinical relevance of copeptin plasma levels as a biomarker of disease severity and mortality in critically ill patients. J. Clin. Lab. Anal., in press., doi: 10.1002/jcla.22614,
• Koch A. , Weiskirchen R., Krusch A., Bruensing J., Buendgens L., Herbers U., Yagmur E., Koek G. H., Trautwein C., Tacke F. (2018): Visfatin serum levels predict mortality in critically ill patients. Dis Markers, 7315356, [2.761]
• Gross A. , Pack L. A. P., Schacht G. M., Kant S., Ungewiss S., Meir M., Schlegel N., Preisinger C., Boor P., Güldiken N., Krusche C. A., Sellge G., Trautwein C., Waschke J., Heuser A., Leube R. E., Strnad P. (2018): Desmoglein 2, but not desmocollin 2, protects intestinal epithelia from injury. Mucosal Immunol, 11, 1630-1639, [7.352]
• Ehedego H. , Mohs A., Jansen B., Hiththetiya K., Sicinski P., Liedtke C., Trautwein C. (2018): Loss of Cyclin E1 attenuates hepatitis and hepatocarcinogenesis in a mouse model of chronic liver injury. Oncogene, 37, 3329-3339, [6.854]
• Cubero F. J. , Peng J., Liao L., Su H., Zhao G., Zoubek M. E., Macias-Rodriguez R., Ruiz-Margain A., Reissing J., Zimmermann H. W., Gassler N., Luedde T., Liedtke C., Hatting M., Trautwein C. (2018): Inactivation of caspase 8 in liver parenchymal cells confers protection against murine obstructive cholestasis. J Hepatol, 69, 1326-1334, [18.946]
• Alsamman, M. , Sterzer, V., Meurer, S. K., Sahin, H., Schaeper, U., Kuscuoglu, D., Strnad, P., Weiskirchen, R., Trautwein, C., Scholten, D. (2018): Endoglin in human liver disease and murine models of liver fibrosis – a protective factor against liver fibrosis. Liver International, 38, 858-867, [4.470]
• Vucur, M. , Roderburg, C., Kaiser, L., Schneider, A.T., Roy, S., Loosen, S., Luedde, M., Trautwein, C., Koch, A., Tacke, F., Luedde, T. (2017): Elevated serum levels of the mixed lineage kinase domain-like protein (MLKL) predict survival of patients during intensive care unit treatment. Hindawi, [2.348]
• Loosen, S.H. , Roderburg, C., Kauertz, K.L., Koch, A., Vucur, M., Schneider, A.T., Binnebösel, M., Ulmer, T.F., Lurje, G., Schoening, W., Tacke, F., Trautwein, C., Longerich, T., Dejong, C.H., Neumann, U.P., Luedde, T. (2017): CEA but not CA19-9 is an independent prognostic factor in patients undergoing resection of cholangiocarcinoma. Scientific Reports, 7, [5.228]
• Hao, F. , Cubero, F.J., Ramadori, P., Liao, L., Haas, U., Lambertz, D., Sonntag, R., Bangen, J.M., Gassler, N., Hoss, M., Streetz, K.L., Reissing, J., Zimmermann, H.W., Trautwein, C., Liedtke, C., Nevzorova, Y.A. (2017): Inhibition of Caspase-8 does not protect from alcohol-induced liver apoptosis but alleviates alcoholic hepatic steatosis in mice. Cell Death & Disease, 8 (10), [5.378]
• Bangen, J.M. , Hammerich, L., Sonntag, R., Baues, M., Haas, U., Lambertz, D., Longerich, T., Lammers, T., Tacke, F., Trautwein, C., Liedtke C. (2017): Targeting CCl4 -induced liver fibrosis by RNA interference-mediated inhibition of cyclin E1 in mice. Hepatology, 66 (4), 1242-1257, [13.246]
• Kuttkat, N. , Mohs, A., Ohl, K., Hooiveld, G., Longerich, T., Tenbrock, K., Cubero, F.J., Trautwein, C. (2017): Hepatic overexpression of cAMP-responsive element modulator α induces a regulatory T-cell response in a murine model of chronic liver disease. BMJ Journals, 66 (5), [14.921]
• Mridha A.R. , Wree A., Robertson A.A.B., Yeh M.M., Johnson C.D., Van Rooyen D.M., Haczeyni F., Teoh N.C., Savard C., Ioannou G.N., Masters S.L., Schroder K., Cooper M.A., Feldstein A.E., Farrell G.C. (2017): NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice. Journal of Hepatology, 66(5), 1037-1046, [10.590]
• Mohs, A. , Kuttkat, N., Reißing, J., Zimmermann, H., Sonntag, R., Proudfoot, A., Youssef, S., de Bruin, A., Cubero, F. J., Trautwein, C. (2017): Functional role of CCL5/RANTES for HCC progression during chronic liver disease. Journal of Hepathology, 66(4), 743–753, [10.590]