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| 1 | Role of interleukin-1 and its antagonism of hepatic stellate cell proliferation and liver fibrosis in the Abcb4^(-/-) mouse model显示文摘AIM: To study the interleukin-1(IL-1) pathway as a therapeutic target for liver fibrosis in vitro and in vivo using the ATP-binding cassette transporter b4^(-/-)(Abcb4^(-/-)) mouse model.METHODS: Female and male Abcb4^(-/-) mice from 6 to 13 mo of age were analysed for the degree of cholestasis(liver serum tests), extent of liver fibrosis(hydroxyproline content and Sirius red staining) and tissue-specific activation of signalling pathways such as the IL-1 pathway [quantitative polymerase chain reaction(q PCR)]. For in vivo experiments, murine hepatic stellate cells(HSCs) were isolated via pronasecollagenase perfusion followed by density gradient centrifugation using female mice. Murine HSCs were stimulated with up to 1 ng/m L IL-1β with or without 2.5 μg/m L Anakinra, an IL-1 receptor antagonist, respectively. The proliferation of murine HSCs was assessed via the Brd U assay. The toxicity of Anakinra was evaluated via the fluorescein diacetate hydrolysis(FDH) assay. In vivo 8-wk-old Abcb4^(-/-) mice with an already fully established hepatic phenotype were treated with Anakinra(1 mg/kg body-weight daily intraperitoneally) or vehicle and liver injury and liver fibrosis were evaluated via serum tests, q PCR, hydroxyproline content and Sirius red staining. RESULTS: Liver fibrosis was less pronounced in males than in female Abcb4^(-/-) animals as defined by a lower hydroxyproline content(274 ± 64 μg/g vs 436 ± 80 μg/g liver, respectively; n = 13-15; P < 0.001; MannWhitney U-test) and lower m RNA expression of the profibrogenic tissue inhibitor of metalloproteinase-1(TIMP)(1 ± 0.41 vs 0.66 ± 0.33 fold, respectively; n = 13-15; P < 0.05; Mann-Whitney U-test). Reduced liver fibrosis was associated with significantly lower levels of F4/80 m RNA expression(1 ± 0.28 vs 0.71 ± 0.41 fold, respectively; n = 12-15; P < 0.05; Mann-Whitney U-test) and significantly lower IL-1β m RNA expression levels(1 ± 0.38 vs 0.44 ± 0.26 fold, respectively; n = 13-15; P < 0.001; Mann-Whitney U-test). No gender differences in the serum liver parameters [bilirubin; alanine aminotransferase(ALT); aspartate aminotransferase and alkaline phosphatase(AP)] were found. In vitro, the administration of IL-1β resulted in a significant increase in HSC proliferation [0.94 ± 0.72 arbitrary units(A.U.) in untreated controls, 1.12 ± 0.80 A.U. at an IL-1β concentration of 0.1 ng/m L and 1.18 ± 0.73 A.U. at an IL-1β concentration of 1 ng/m L in samples from n = 6 donor animals; P < 0.001; analyses of variance(ANOVA)]. Proliferation was reduced significantly by the addition of 2.5 μg/m L Anakinra(0.81 ± 0.60 A.U. in untreated controls, 0.92 ± 0.68 A.U. at an IL-1β concentration of 0.1 ng/m L, and 0.91 ± 0.69 A.U. at an IL-1β concentration of 1 ng/m L; in samples from n = 6 donor animals; P < 0.001; ANOVA) suggesting an anti-proliferative effect of this clinically approved IL-1 receptor antagonist. The FDH assay showed this dose to be non-toxic in HSCs. In vivo, Anakinra had no effect on the hepatic hydroxyprolinecontent, liver serum tests(ALT and AP) and profibrotic(collagen 1α1, collagen 1α2, transforming growth factor-β, and TIMP-1) and anti-fibrotic [matrix metalloproteinase 2(MMP2), MMP9 and MMP13 ] gene expression after 4 wk of treatment. Furthermore, the hepatic IL-1β and F4/80 m RNA expression levels were unaffected by Anakinra treatment.CONCLUSION: IL-1β expression is associated with the degree of liver fibrosis in Abcb4^(-/-) mice and promotes HSC proliferation. IL-1 antagonism shows antifibrotic effects in vitro but not in Abcb4^(-/-) mice. | Florian P Reiter Ralf Wimmer Lena Wottke Renate Artmann Jutta M Nagel Manuel O Carranza Doris Mayr Christian Rust Peter Fickert Michael Trauner Alexander L Gerbes Simon Hohenester Gerald U Denk | 2016 | World Journal of Hepatology2016，8，8： | 3 |
| 2 | Classification of types of intraductal papillary-mucinous neoplasm of the pancreas: a consensus study显示文摘 | Toru Furukawa Günter Kl?ppel N. Volkan Adsay Jorge Albores-Saavedra Noriyoshi Fukushima Akira Horii Ralph H. Hruban Yo Kato David S. Klimstra Daniel S. Longnecker Jutta Lüttges G. Johan A. Offerhaus Michio Shimizu Makoto Sunamura Arief Suriawinata Kyoichi | 2005 | Virchows Archiv2005，，5： | 3 |
| 3 | Surgery for Ductal Adenocarcinoma of the Pancreatic Head: Staging, Complications, and Survival after Regional versus Extended Lymphadenectomy显示文摘 | Doris Henne-Bruns Ilka Vogel Jutta Lüttges Günter Kl?ppel Bernd Kremer | 2000 | World Journal of Surgery2000，，5： | 2 |
| 4 | Histopathological features of diagnostic and clinical relevance in autoimmune pancreatitis: a study on 53 resection specimens and 9 biopsy specimens显示文摘 | Giuseppe Zamboni Jutta Lüttges Paola Capelli Luca Frulloni Giorgio Cavallini Paolo Pederzoli Alexander Leins Daniel Longnecker Günter Kl?ppel | 2004 | Virchows Archiv2004，，6： | 1 |
| 5 | Sorption of tetracycline and chlortetracycline on K-and Ca-Saturated soil clays, humic substances, and Clay-Humic complexes 显示文摘 | Jutta R V P David A L | 2007 | Environ Sci Technol2007，41，： | 1 |
| 6 | Effect of the novel anxiolytic drug deramciclane on cytochrome P450 2D6 activity as measured by desipramine pharmacokinetics显示文摘 | Kari L Steven DB Harry B Juha R Jutta H Harry S | 2004 | Eur J Clin Pharmacol2004，59，： | 1 |
| 7 | Marked resistance of RARγ-deficient mice to the toxic effects of retinoic acid显示文摘 | Jutta L Landwehr J Bauer F | 1995 | the American physiological Society1995，193，： | 1 |
| 8 | Nuclear factor-eythroid 2-related factor 2 prevents alcohol-induced fulmlnant liver injury 显示文摘 | Jutta L Silke M JUrgen B | 2008 | Gastroenterology2008，134，4： | 1 |
| 9 | Porcine mannan-binding lectin A binds to actinobacillus snis and Hatmophilus parasuu显示文摘 | Brandon N L Jutta D H Janet I M | 2006 | Developmental and Comparative Immunology2006，30，： | 1 |
| 10 | Porcine mannan-binding lectin A bind to Actinobacillus suis and Haemophilus parasuis显示文摘 | Brandon N L Jutta D H Janet I M | 2006 | Developmental and comparative immunology2006，30，10： | 1 |
| 11 | Surgery for Ductal Adenocarcinoma of the Pancreatic Head: Staging, Complications, and Survival after Regional versus Extended Lymphadenectomy显示文摘 | Doris Henne-Bruns Ilka Vogel Jutta Lüttges Günter Kl?ppel Bernd Kremer | 2000 | World Journal of Surgery2000，，5： | 1 |
| 12 | Histopathological features of diagnostic and clinical relevance in autoimmune pancreatitis: a study on 53 resection specimens and 9 biopsy specimens显示文摘 | Giuseppe Zamboni Jutta Lüttges Paola Capelli Luca Frulloni Giorgio Cavallini Paolo Pederzoli Alexander Leins Daniel Longnecker Günter Kl?ppel | 2004 | Virchows Archiv2004，，6： | 1 |
| 13 | Histopathological features of diagnostic and clinical relevance in autoimmune pancreatitis: a study on 53 resection specimens and 9 biopsy specimens显示文摘 | Giuseppe Zamboni Jutta Lüttges Paola Capelli Luca Frulloni Giorgio Cavallini Paolo Pederzoli Alexander Leins Daniel Longnecker Günter Kl?ppel | 2004 | Virchows Archiv2004，，6： | 1 |
| 14 | Kinetics of DNA strand breaks and protection by antioxidants in UVA-or UVB- irradiated HaCaT keratinocytes using the single cell gel electrophoresis assay 显示文摘 | Dieter P Stefan P | 1998 | Mutation Research1998，407，： | 1 |
| 15 | aRNA-longSAGE:a new approach to generate SAGE libraries from microdissected cells显示文摘 | Heidenblut Jutta Lüttges | 2004 | Nucleic Acids Research2004，32，16： | 1 |
| 16 | Nuclear factor,eythroid 2-related fac-tor 2 prevents alcohol-induced fulminant liver injury 显示文摘 | Jutta L Silke M Jargen B | 2008 | Gastroen- terology2008，134，： | 1 |
| 17 | Nuclear factor-eythroid 2-related factor 2 prevents alcohol-induced fulminant liver injury 显示文摘 | Jutta L Silke M Ju rgen B | 2008 | Gastroenterology2008，134，4： | 1 |
| 18 | Histopathological features of diagnostic and clinical relevance in autoimmune pancreatitis: a study on 53 resection specimens and 9 biopsy specimens显示文摘 | Giuseppe Zamboni Jutta Lüttges Paola Capelli Luca Frulloni Giorgio Cavallini Paolo Pederzoli Alexander Leins Daniel Longnecker Günter Kl?ppel | 2004 | Virchows Archiv2004，，6： | 1 |
| 19 | Porcine mannan-binding lectin A bind to Actinobacillus suis and Haemophilus parasuis 显示文摘 | BRANDON N L JUTTA D H JANET I M | 2006 | Developmental and Comparative Immunology2006，30，： | 1 |
| 20 | Classification of types of intraductal papillary-mucinous neoplasm of the pancreas: a consensus study显示文摘 | Toru Furukawa Günter Kl?ppel N. Volkan Adsay Jorge Albores-Saavedra Noriyoshi Fukushima Akira Horii Ralph H. Hruban Yo Kato David S. Klimstra Daniel S. Longnecker Jutta Lüttges G. Johan A. Offerhaus Michio Shimizu Makoto Sunamura Arief Suriawinata Kyoichi | 2005 | Virchows Archiv2005，，5： | 1 |
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