|
|
|
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 | The physics of granular materials显示文摘 | Jaeger H M Nagel S R Behringer R P | 1996 | Physics Today1996，49，4： | 1 |
| 3 | Serum cholesterol and mortality in patients with multiple organ failure显示文摘 | Fraunberger P Nagel D Walli AK | 2000 | Crit Care Med2000，28，： | 1 |
| 4 | Biochemical complementation of chalcone synthase mutants defines a role for flavonols in functional pollen显示文摘 | Mo Y Nagel C Taylor L P | 1992 | Proceedings of the National Academy of Sciences1992，89，15： | 1 |
| 5 | Still flow- ing approaches on traffic flow and traffic jam model- ing显示文摘 | NAGEL K WAGNER P WOESLER R | 2003 | Operations Research2003，51，5： | 1 |
| 6 | Tobacco-specific Nitrosamines accumulation and distribution in flue-cured tobacco显示文摘 | POUR P ALTHOFF J NAGEL D | 1977 | Cancer Lett1977，3，： | 1 |
| 7 | Still flowing:ap-proaches to traffic flow and traffic jam modeling显示文摘 | Nagel K Wagner P Woesler R | 2003 | Operations Research2003，51，5： | 1 |
| 8 | Formation of nitric oxide, super-oxide, and peroxynitein myocardial ischemia-reperfusion injury in rats显示文摘 | Liu P Hock CE Nagele R | 1997 | Am J Physiol1997，272，52： | 1 |
| 9 | Air pollution and lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE) 显示文摘 | Raaschou-Nielsen 0 Andersen ZJ Beelen R Samoli E Stafoggia M Weinmayr G Hoffmann B Fischer P Nieuwenhuijsen MJ Brunekreef B Xun WW Katsouyanni K Dimakopoulou K Sommar J Forsberg B Modig L Oudin A Oftedal B Schwarze PE Nafstad p De Faire U Pedersen NL Ostenson CG Fratiglioni L Penell J Korek M Pershagen G Eriksen KT Serensen M Tjenneland A Ellermann T Eeftens M Peeters PH Meliefste K Wang M Bueno-de-Mesquita B Key TJ de Hoogh K Concin H Nagel G Yilier A Grioni S Krogh y Tsai MY Ricceri F Sacerdote C Galassi C Migliore E Ranzi A Cesaroni G Badaloni C Forastiere F Tamayo I Amiano P Dorronsoro M Trichopoulou A Bamia C Yineis p Hoek G | 2013 | Lancet Oncol2013，14，9： | 1 |
| 10 | Augmentation of nitric oxide,superoxide and peroxynitrite production during cerebral ischemia and reperfusion in the rat显示文摘 | FormanL Liu J P Nagele RG | 1998 | Neurochem Res1998，23，： | 1 |
| 11 | A theoretical study of the electronic structure and bonding of the monoclinic phase of Mg2NiH4显示文摘 | JASEN P V GONZALEZ E Z BRIZUELA G NAGEL O A GONZALEZ G A JUAN A | 2007 | International Journal of Hydrogen Energy2007，32，18： | 1 |
| 12 | Serum Cholesterol and Mortality in Patients with Multiple Organ Failure显示文摘 | Fraunberger P Nagel D Walli A K | 2000 | Crit Care Med2000，28，10： | 1 |
| 13 | Integrated planar terahertz resonators for femtomolar sensitivity label-free detection of DNA hybr-idization显示文摘 | NAGEL M BOLIVAR P H BRUCHERSEIFER M | 2002 | Appl Optics2002，41，10： | 1 |
| 14 | Microbial system for identification of antibiotic residues in milk 显示文摘 | NAGEL O MOLINA P ALTHAUS R | 2011 | J Food Drug Anal2011，19，3： | 1 |
| 15 | Inhibition of nitric oxide synthase attenuates peroxynitrite generation,but augments neutrophil accumulation in hepatic ischemia-reperfusion in rats显示文摘 | Liu P Yin K Nagele R | 1998 | J Pharmacol Exp Ther1998，284，3： | 1 |
| 16 | DyIlamie Simulation and Energy Absorption of Tapered Thin · walled Tubes Under Oblique Impact Loading显示文摘 | Nagel G M Thambiratnam D P | | 0，，： | 1 |
| 17 | A review of the specific role of oxygen in irreversible photo- and thermally induced changes of the optical properties of thin film amorphous chalcogenides 显示文摘 | TICHY L TICHA H NAGELS P | 1995 | Opt Mater1995，4，6： | 1 |
| 18 | Serum cholesterol and mortality in patients with multiple organ failure显示文摘 | Fraunberger P Nagel D Walli AK | 2000 | Crit Care Med2000，28，10： | 1 |
| 19 | Integrated THz technology for label - free genetic diagnostics 显示文摘 | Nagel M Bolivar P H Brucherseifer M | 2002 | Appl Phys Lett2002，80，： | 1 |
| 20 | Estrogenic pesticides:binding relative to estradiol in MCF-7 cells and effects of exposure during fetal life on subsequent territorial behaviour in male mice显示文摘 | F S vom Saal S C Nagel P Palanza | 1995 | Toxicology Letters1995，17，： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员