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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 | 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 |
| 3 | Sulfate-reducing bacterial community response to carbon source amendments in contaminated aquifer microcosms显示文摘 | Jutta K Oliver P Martin H S | 2002 | FEMS Microbiology Ecology2002，42，： | 1 |
| 4 | 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 |
| 5 | Protection of chickens against H5N1 highly pathogenic avian influenza virus infection by live vaccination with infectious laryngotracheitis virus recombinants expressing H5 hemagglutinin and N1 neuraminidase显示文摘 | Sophia P Pavlova Jutta Veits Günther M Keil | 2009 | Vaccine2009，27，： | 1 |
| 6 | Kynurenine 3-Hydroxylase Inhibition in Rats: Effects on Extracellular Kynurenic Acid Concentratin and N-Methyl-D-Aspartate-Induced Deplarisation in the Striatum显示文摘 | Tihomir P Obrenovitch | 2000 | J Neurochem2000，75，6： | 1 |
| 7 | Protection of chickens against H5N1 highly pathogenic avian influenza virus in- fection by live vaccination with infectious laryngotracheitis virus re- combinants expressing H5 hemagglutinin and N1 neuraminidase 显示文摘 | SOPHIA P P JUTTA V GUNTHER M K | 2009 | Vaccine2009，27，： | 1 |
| 8 | Modelling vertical migration of the cyanobacterium Microcystis 显示文摘 | Petra M V Jutta P Luuc R M | 1997 | Hydrobiologia1997，349，： | 1 |
| 9 | Di- fferent responses of E/Z-isomers of pesticides in liquid chromatography-electrospray ionization- mass spectrometry 显示文摘 | BERNHARD M H LUDWIG H JUTTA P | 2010 | Journal of Mass Spec- trometry2010，45，7： | 1 |
| 10 | The Prognostic Value of Lymph Node Ratio in a Population-Based Collective of Colorectal Cancer Patients显示文摘 | Robert Rosenberg Jutta Engel Christiane Bruns Wolfgang Heitland Nikolaus Hermes Karl-Walter Jauch Reinhard Kopp Eberhard Pütterich Reinhard Ruppert Tibor Schuster Helmut Friess Dieter H?lzel | 2010 | Annals of Surgery2010，，6： | 1 |
| 11 | Developing Internet Ecommerce Benchmarks 显示文摘 | Jutta D Bodorik P Wang Y | 1999 | Information System1999，24，6： | 1 |
| 12 | The multi-protein family of Arabidnpsis sulpho- transferases and their relatives in other plant species 显示文摘 | Marion K Jutta P | 2004 | Journal of Experimental Botany2004，55，： | 1 |
| 13 | 临床中急性乳腺炎对奶牛行为的影响显示文摘急性乳腺炎是高产奶牛最常见的疾病之一。然而目前仍然缺乏在急性乳腺炎初期行为变化的精确认知,这些行为变化是否能应用于临床乳腺炎的早期检测更是有待研究。此外,乳腺炎可在行为的优先次序上引起奶牛相关的行为冲突,从而扰乱病态行为的经典模式:奶牛可能由于乳房疼痛不舒服引起横卧行为的增加。为研究此问题,试验监测6头由于内毒素诱导而患有急性乳腺炎的奶牛的行为。对奶牛行为从诱导前1d(对照日)到诱导后24h(诱导日)进行拍摄。为了对此炎症进行后续研究,采取牛奶样品并定期检查奶牛的健康状况。除了加强和护理身体外,每天持续观察和确定所有的行为,并进行频率计数。对于站立和横卧行为的持续时间进行分析。为了检验诱导时间对乳腺炎的的影响,数据相应以2h为时间间隔划分。试验采用重复观测方法对由于诱导产生奶牛所有行为的变化以及行为的线性变化规律的混合模式进行分析。与诱导前1d相比,诱导日中总体奶牛横卧时间要减少,并在一侧乳房发炎的群体中横卧时间也相对降低。奶牛在诱导日中要花较长时间采食青贮,并且其采食节奏比前1d要快。当奶牛乳房严重肿胀并发高烧时,其横卧和反刍的时间更加下降,同时饮水减少。试验总结出不同于典型的病态行为,奶牛并没有增加其横卧时间,而是站立时间更多,并且避免在乳房发炎一侧横卧。试验提示乳房炎的疼痛刺激了奶牛疾病的行为状态。新的乳腺炎检测工具应能自动检测其行为变化并结合生理参数(如发烧)和行为上的休息、站立以及饮食行为组成其变化的模式。 | Jutta S Suvi T Mari H Matti P Joop B L Satu P Laura H | 2011 | 饲料博览2011，，8： | 0 |
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