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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 | RANKL/RANK control Brca1 mutation-driven mammary tumors显示文摘 | Verena Sig Kwadwo Owusu-Boaitey Puma A Joshi Anoop Kavirayani Gerald Wimsberger Maria Novatchkova Ivona Kozieradzki Daniel Schramek Nnamdi Edokobi Jerome Hersl Aishia Sampson Ashley Odai-Afotey Conxi Lazaro Eva Gonzalez-Suarez Miguel A Pujaaa for CIMBA Holger Heyn Enrique Vidal Jennifer Cru. ickshank Hal Berman Renu Sarao Melita Tieevic Iris Uribesalgo Luigi Tortola Shuan Rao Yen Tan Georg Pfeiler Eva YHP Lee Zsuzsanna Bago-Horvath Lukas Kenner Helmuth Popper Christian Singer Rama Khokha LaundeRe P Jones Josef M Penninger | 2016 | Cell Research2016，26，7： | 3 |
| 3 | A novel method for the growth of Silicalite membranes on stainless steel supports显示文摘 | Stuart H Christian M M Richard P | 1999 | Chem Mater1999，11，： | 1 |
| 4 | Males outcompete hermaphrodites for seed siring success in controlled crosses in the polygamous Fraxinus excelsior (Oleaceae)显示文摘 | MARIE-ELISE M P CHRISTIAN R | | 0，，06： | 1 |
| 5 | 查看详情显示文摘 | Torben S Thomas M Kjartan F Sφren L F Christian P | | 0，，： | 1 |
| 6 | A vector - perturbation technique for near - capacity multi antenna mul- tiuser communication part II : perturbation 显示文摘 | BERTRAND M H CHRISTIAN B P LEE S A | 2005 | Communica- tions IEEE Transactions2005，53，7： | 1 |
| 7 | Influence of heart rate, blood pressure, and beta-blocker dose on outcome and the difference in outcome between carvedilol and metoprolol tartrate in patients with chronic heart failure: results form the COMET trial显示文摘 | MARCO M CHRISTIAN T P KARL S | 2005 | Eur Heart J2005，26，21： | 1 |
| 8 | A vector - perturbation technique for near - capacity multi antenna mul- tiuser communication Part I : channel inversion and regulari- zation 显示文摘 | BERTRAND M H CHRISTIAN B P A LEE S | 2005 | IEEE Transactions on Communication2005，53，9： | 1 |
| 9 | Degrad-ability of black carbon and its impact on trace gas fluxes andcarbon turnover in paddy soils 显示文摘 | Christian K Arina-Ann M Eva-Maria P | 2011 | Soil Biology and Bio-chemistry2011，43，9： | 1 |
| 10 | FGF23 induces left ventricular hypertrophy显示文摘 | Faul Christian Amaral Ansel P Oskouei Behzad Hu Ming-Chang Sloan Alexis Isakova Tamara Gutiérrez Orlando M Aguillon-Prada Robier Lincoln Joy Hare Joshua M Mundel Peter Morales Azorides Scialla Julia Fischer Michael Soliman Elsayed Z Chen J | 2011 | Journal of Clinical Investigation2011，，11： | 1 |
| 11 | Promising new agents under development by the division of cancer treatment, diagnosis, and centers of the national cancer institute 显示文摘 | Pluda J M Ho P T | 1997 | Semin Oncol1997，24，2： | 1 |
| 12 | Magnetic resonance classification of lumbar intervertebral disc degeneration显示文摘 | Christian W A P Alexander M Marco Z | 2001 | Spine2001，26，17： | 1 |
| 13 | Denoising NMR time-domain sig- nal by singular-value decomposition accelerated by graphics processing unites显示文摘 | Pascal P M Christian B Florence B | 2014 | Solid State Nuclear Magnetic Resonance2014，61，5： | 1 |
| 14 | Probabilistic flow pattern-based heat transfer correlation for condensing intermittent flow of refrigerants in smooth horizontal tubes 显示文摘 | van Rooyen E Christians M Liebenberg L Meyer J P | 2010 | International Journal of Heat and Mass Transfer2010，53，： | 1 |
| 15 | Effective primary isolation of wild-type Canine distemper virus in MDCK, MV1 Lu and Vero cells without nucleotide sequence changes within the entire haemagglutinin protein gene and in subgenomic sections of the fusion and phospho protein genes显示文摘 | John A Lednicky Thomas P Meehan Michael J Kinsel Jean Dubach Laura L Hungerford Nicolene A Sarich Kelley E Witecki Michael D Braid Casandra Pedrak Christiane M Houde | 2004 | Journal of Virological Methods2004，，2： | 1 |
| 16 | An Improved Optimization Algorithm and a Bayes Factor Termination Criterion for Sequential Projection Pursuit显示文摘 | Bobbie J M Webb-Robertson Kristin H J Scott D H Christian P Bob W W | 2005 | Chemometrics and Intelligence Laboratory Systems2005，77，12： | 1 |
| 17 | Nutri- ent regulation of bacterial production and ectoenzyme ac- tivities in the subtropical North Pacific Ocean显示文摘 | DONACHIE S P CHRISTIAN J R KARL D M | 2001 | Deep Sea Research Part II: Topical Studies in Oceanography2001，48，8： | 1 |
| 18 | Promising designs of compact heat exchangers for modular HTRs using the Brayton cycle显示文摘 | Franck P Patrice T Christian M | 2008 | Nuclear Engineering and Design2008，238，11： | 1 |
| 19 | Expression and redistribution of cellular Bad, Bax, and Bcl-XL protein is associated with VCD-induced ovotoxicity in rats 显示文摘 | Hu X M Christian P Sipes I G | 2001 | Biol Reprod2001，65，5： | 1 |
| 20 | Identification and population dynamics of yeasts in sourdough fermentation processes by PCR-denaturing gradient显示文摘 | Christiane B M Walter P H Christian H | 2003 | Applied and Environmental Microbiology2003，，12： | 1 |
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