|
|
|
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 | Early atherosclerosis in obese is associated with low serum levels of adiponectin显示文摘 | Stefan P Renate H Reinhard M | 2005 | J Clin Endocrinol Metab2005，90，8： | 1 |
| 3 | Ex vivo gene transfer in the years to come显示文摘 | Thomas P Renate E G Ulf M | 2002 | Arthritis Res2002，4，： | 1 |
| 4 | Bacteriocin-like substance production by Carnobacterium piscicola in a continuous system with three culture broths study of antagonism against Listeria monocytogenes on vacuum packaged salmon显示文摘 | Renate P Schobitz Pamela A Borquez | 2006 | Brazilian Journal of Microbiology2006，37，1： | 1 |
| 5 | Analysis of a regulatory element in the 5P-untranslated region of the bcl-2gene显示文摘 | Ines K Renate W Peter P | 1997 | FEBS Letters1997，406，： | 1 |
| 6 | Early athero sclerosis in obese juveniles is associated with low serum levels of adiponectin显示文摘 | STEFAN P RENATE H REINHARD M | 2005 | J Clin Endocrinol Metabolism2005，90，8： | 1 |
| 7 | Origins of' late' relapse in childhood acute lymphoblastic leukemia with TEL-AML1 fusion genes显示文摘 | Anthony M Karin F Renate P | 2001 | Blood2001，98，3： | 1 |
| 8 | Bacteriocin-like substance production by Carnobacterium piscicola in a continuous system with three culture broths study of antagonism against Listeria monocytogenes on vacuum packaged salmon显示文摘 | Renate P Schobitz Pamela A Borquez | 2006 | Brazilian Journal of Microbiology2006，37，1： | 1 |
| 9 | Analysis of a regulatory element in the 5'-untranslated region of the bcl-2 gene显示文摘 | Ines K Renate W Peter P | 1997 | FEBS Letters1997，406，： | 1 |
| 10 | Tumor necrosis factor-alpha:alternative role as an inhibitor of osteoclast formation in vitro显示文摘 | Renate B Antoinette W Jeannette P | 2006 | Bone2006，39，2： | 1 |
| 11 | Part-whole Relationship Categories and Their Application in Object-oriented Analysis 显示文摘 | RENATE M P JENS K | 1999 | IEEE Transactions on Knowledge and Data Engineering1999，11，5： | 1 |
| 12 | Bacteriocin-like Substance Production by Camobacterium piscicola in a Continuous System with Three Culture Broths Study of Antagonism Against Listeria monocytogenes on Vacuum Packaged Salmon显示文摘 | RENATE P S PAMELA A B | 2006 | Brazilian Journal of Microbiology2006，37，1： | 1 |
| 13 | Raman spectroscopy A prospective tool in the life sciences 显示文摘 | Renate P Michael S Jtirgen P | 2003 | ChemPhysChem2003，4，1： | 1 |
| 14 | Cardiac performance in the zebrafish breakdance mutant显示文摘 | Renate K Thorsten S Bernd P etal | 2005 | J Exp Biol2005，208，： | 1 |
| 15 | Integerated log interpretation in the German Continental Deep Drilling Program:Lithology,porosity and fracture zones,The KTB deep drill hole显示文摘 | Renate P Susanne H Jurgen W | 1997 | Journal of Geophysical Research1997，102，8： | 1 |
| 16 | Antibacterial Surface Coatings from Zinc Oxide Nanoparticles Embedded in Poly( N ‐isopropylacrylamide) Hydrogel Surface Layers显示文摘 | Véronique B. Schwartz Franck Thétiot Sandra Ritz Sabine Pütz Lars Choritz Alexandros Lappas Renate F?rch Katharina Landfester Ulrich Jonas | 2012 | Adv. Funct. Mater2012，，11： | 1 |
| 17 | Luth (2009) From Building Information Model to Building Knowledge Model显示文摘 | Renate Fruchter Tim Sehrotenboer and Gregory P | 2009 | Computing in Civil Engineering2009，，： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员