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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 | The effect of desalivation on the malignant transformation of the tongue epithelium and associated stromal myofibroblasts in a rat 4- nitroquinoline 1-oxide-induced carcinogenesis model显示文摘 | Vered M Grinstein-Koren O Reiter S | 2010 | Int J Exp Pathol2010，91，4： | 1 |
| 3 | Antibodies and their fragments as anti-cancer agents显示文摘 | Schaedel O Reiter Y | 2006 | Curr Pharrm Des2006，12，3： | 1 |
| 4 | Biomarker validation in blood specimens by selected reaction monitoring mass spectrometry of N-glycosites显示文摘 | Ossola R Schiess R Picotti P Rinner O Reiter L Aebersold R | | 0，，： | 1 |
| 5 | mProphet:automated data processing and statistical validation for large-scale SRM experiments 显示文摘 | REITER L RINNER O PICOTTI P | 2011 | Nature Methods2011，8，5： | 1 |
| 6 | Symmetric attractors in three-dimensional space显示文摘 | Brisson G F Gartz K M McCune B J O' Brien K P Reiter C A | 1996 | Chaos Solitons & Fractals1996，7，7： | 1 |
| 7 | A comparison of interferon-conl with natural recombinant interferons-α: Antiviral, antiproliferative,and natural killer-inducing activities 显示文摘 | Ozes O N Reiter Z Klein S | 1992 | Journal of Interferon Research1992，12，1： | 1 |
| 8 | Treatments for cutaneous lichen planus: a systematic review and Meta-analysis 显示文摘 | Atzmony L Reiter O Hodak E | 2016 | Am J Clin Dermatol2016，17，1： | 1 |
| 9 | Antibodies and their fragments as anti-cancer agents 显示文摘 | SCHAEDEL O REITER Y | 2006 | Curr Pharm Des2006，12，3： | 1 |
| 10 | A comparison of interferon-Con1 with natural recombinant interferons-alpha:antiviral,antiproliferative,and natural killer-inducing activities显示文摘 | Ozes O N Reiter Z Klein S | | 0，，01： | 1 |
| 11 | Enzymatic cleavage of lignin β-O-4 aryl ether bonds via net internal hydrogen transfer显示文摘 | REITER J STRITTMATTER H WIEMANN L O | 2013 | Green Chemistry2013，15，5： | 1 |
| 12 | Structure-property-performance relations of high-rate reactive arc-evaporated Ti-B-N nanocomposite coatings 显示文摘 | NEIDHARDT J O'SULLIVAN M REITER A E | 2006 | Surface and Coatings Technology2006，201，6： | 1 |
| 13 | Probe manipulators for Wendelstein 7-X and their interaction with the magnetic topology显示文摘Probe manipulators are a versatile addition to typical plasma edge diagnostics.Equipped with material samples they allow for detailed investigation of plasma–wall interaction processes,such as material erosion,deposition or impurity transport pathways.When combined with electrical probes,a study of scrape-off layer and plasma edge density,temperature and flow profiles as well as magnetic topologies is possible.A mid-plane manipulator is already in operation on Wendelstein 7-X.A system in the divertor region is currently under development.In the present paper we discuss the critical issue of heat and power loads,power redistribution and experimental access to the complex magnetic topology of Wendelstein 7-X.All the aforementioned aspects are of relevance for the design and operation of a probe manipulator in a device like Wendelstein?7-X.A focus is put on the topological region that is accessible for the different coil current configurations at Wendelstein 7-X and the power load on the manipulator with respect to the resulting different magnetic configurations.Qualitative analysis of power loads on plasma-facing components is performed using a numerical tracer particle diffusion tool provided via the Wendelstein 7-X Webservices. | M RACK D HOSCHEN D REITER B UNTERBERG J W COENEN S BREZINSEK O NEUBAUER S BOZHENKOV G CZYMEK Y LIANG M HUBENY Ch LINSMEIER the Wendelstein 7-X Team | 2018 | Plasma Science and Technology2018，20，5： | 0 |
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