|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 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 | Crowds显示文摘 | Michael K. Reiter Aviel D. Rubin | 1998 | ACM Transactions on Information and System Security (TISSEC)1998，，1： | 2 |
| 3 | False data injection attacks against state estimation in electric power grids显示文摘 | Yao Liu Peng Ning Michael K. Reiter | 2011 | ACM Transactions on Information and System Security (TISSEC)2011，，： | 1 |
| 4 | The WTO Ministerial Conference-The committee on Trade and Environment:Highlights of the Report to Ministers and Outlook on Future Work显示文摘 | Reiterer | 1997 | Australian Review of International and European law1997，，： | 1 |
| 5 | False data injection attacks against state estimation in electric power grids显示文摘 | Yao Liu Peng Ning Michael K. Reiter | 2011 | ACM Transactions on Information and System Security (TISSEC)2011，，1： | 1 |
| 6 | Crowds:Anonymity for Web Transactions显示文摘 | MICHAEL K REITER AVIEL D Rubin | 1998 | ACM Transactions on Information and System Security1998，1，1： | 1 |
| 7 | Byzantine quorum systems显示文摘 | Dahlia Malkhi Michael Reiter | 1998 | Distributed Computing1998，，4： | 1 |
| 8 | Crowds: Anonymity for web transactions显示文摘 | Michael Reiter Aviel Rubin | 1998 | ACM Transactions on Information and System Security1998，，1： | 1 |
| 9 | 1,25-(OH) 2 -vitamin D 3 prevents activation of hepatic stellate cells in vitro and ameliorates inflammatory liver damage but not fibrosis in the Abcb4 ?/? model显示文摘 | Florian P. Reiter Simon Hohenester Jutta M. Nagel Ralf Wimmer Renate Artmann Lena Wottke Marie-Christine Makeschin Doris Mayr Christian Rust Michael Trauner Gerald U. Denk | 2015 | Biochemical and Biophysical Research Communicatio2015，，2： | 1 |
| 10 | High-Sensitivity Cardiac Troponin in the Distinction of Acute Myocardial Infarction From Acute Cardiac Noncoronary Artery Disease显示文摘 | Philip Haaf Beatrice Drexler Tobias Reichlin Raphael Twerenbold Miriam Reiter Julia Meissner Nora Schaub Claudia Stelzig Michael Freese Amely Heinzelmann Christophe Meune Cathrin Balmelli Heike Freidank Katrin Winkler Kris Denhaerynck Willibald Hochholzer | 2012 | Circulation2012，，1： | 1 |
| 11 | Anonymous Web trans- actions with crowds 显示文摘 | Reiter Michael K Rubin Aviel D | 1999 | Communications of the ACM1999，42，2： | 1 |
| 12 | Resilient Authentication Usfng Path Independence显示文摘 | Michael K Reiter Stuart G Stubblebine | 1998 | IEEE Transactions on Computers1998，47，12： | 1 |
| 13 | Ring-opening metathesis polymerization for the preparation of norbornene-based weak cation-exchange monolithic capillary columns显示文摘 | Christina Gatschelhofer Agnes Mautner Franz Reiter Thomas R. Pieber Michael R. Buchmeiser Frank M. Sinner | 2008 | Journal of Chromatography A2008，，13： | 1 |
| 14 | N-terminal Pro B-type Natriuretic Peptide in the Early Evaluation of Suspected Acute Myocardial Infarction显示文摘 | Philip Haaf Cathrin Balmelli Tobias Reichlin Raphael Twerenbold Miriam Reiter Julia Meissner Nora Schaub Claudia Stelzig Michael Freese Patricia Paniz Christophe Meune Beatrice Drexler Heike Freidank Katrin Winkler Willibald Hochholzer Christian Mueller | 2011 | The American Journal of Medicine2011，，8： | 1 |
| 15 | Hope and Expectancy in Solution - Focused Brief Therapy 显示文摘 | Reiter Michael D | 2010 | Journal of Family Psychotherapy2010，21，2： | 1 |
| 16 | Robotic-assisted transhiatal esophagectomy显示文摘 | Carsten N. Gutt Vasile V. Bintintan J?rg K?ninger Beat P. Müller-Stich Michael Reiter Markus W. Büchler | 2006 | Langenbeck’s Archives of Surgery2006，，4： | 1 |
| 17 | Crowds: anonymity for web transactions显示文摘 | Michael K Reiter Aviel D | 1998 | ACM Transaction on Information and System Security1998，19，： | 1 |
| 18 | Decreased EEG coherence between prefrontal electrodes: a correlate of high language proficiency?显示文摘 | Susanne Reiterer Michael L. Berger Claudia Hemmelmann Peter Rappelsberger | 2005 | Experimental Brain Research2005，，1： | 1 |
| 19 | Thiazolidinedione Drugs Promote Onset, Alter Characteristics, and Increase Mortality of Ischemic Ventricular Fibrillation in Pigs显示文摘 | Mohammad Sarraf Li Lu Shuyu Ye Michael Reiter Clifford Greyson Gregory Schwartz | 2012 | Cardiovascular Drugs and Therapy2012，，3： | 1 |
| 20 | Resilient Authentication Using Path Independence显示文摘 | Michael K Reiter Stuart G Stubblebine | 1998 | IEEE Transactions on Computers1998，47，12： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员