|
|
|
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 | Surgery versus radiation theapy for patients with aggressive fibromatosis or desmoid tumors: a comparative review of 22 articles 显示文摘 | NUYTTENS J J RUST P F THOMAS J R C R | 2000 | Cancer2000，88，： | 1 |
| 3 | Influence of Bone-Lead stores on the observed effectiveness of lead harzad intervention显示文摘 | Rust SW Kumar P Burgoon DA | 1999 | Environ Res1999，81，： | 1 |
| 4 | E-Service: a new Para- digm for Business in the Electronic Environment 显示文摘 | Rust R T Kannan P K | 2003 | Communications of the ACM2003，46，6： | 1 |
| 5 | Influence of bone-lead stores on the observed effectiveness of lead hazard intervention显示文摘 | Rust SW Kumar P Burgoon DA | 1999 | Environ Res1999，81，： | 1 |
| 6 | Human papilloma virus (HPV) -E6/E7 and epidermal growth factor receptor(EGFR) protein levels in cervical cancer and cervical intraepithelial neoplasia (CIN) 显示文摘 | Mathur SP Mathur RS Rust P | 2001 | Am J Reprod Immunol2001，46，4： | 1 |
| 7 | Fatigue cracking resistance of fiber reinforced asphalt concrete显示文摘 | Lee S J Rust J P Hamouda Hechmi | 2005 | Textile Research Journal2005，75，2： | 1 |
| 8 | Hepatocyte apoptosis after bile duct ligation in the mouse involves fas显示文摘 | MIYOSHI H RUST C ROBERTS P J | 1999 | Gastroenteroly1999，117，： | 1 |
| 9 | A ballon-borne telescope for high resolution solar imaging and polarimetry显示文摘 | BERNASCONI P N RUST D M EATON H A | 2000 | SPIE2000，4014，： | 1 |
| 10 | Surgery versus radiation therapy for patients with aggressive fibromatosis or desmoid tumors: a comparative review of 22 articles显示文摘 | Nuyttens J J Rust P F Thomas C R Jr | 2000 | Cancer2000，88，7： | 1 |
| 11 | Fatigue cracking resistance of fiber-reinforced asphalt concrete 显示文摘 | LEE S J RUST J P HAMOUDA H KIM Y R BORDEN R H | 2005 | Textile Research Journal2005，75，2： | 1 |
| 12 | ProblemSolving Learning Environments and Assessment; AKnowledge Space Theory Approach 显示文摘 | REIMANN P RUST M K ALBERT D | 2013 | ComputerEducation2013，64，3： | 1 |
| 13 | Influenced of bone lead stores on the observed effectiveness of lead hazard intervention显示文摘 | Rust S W Kumar P Burgoon D A | 1999 | Environ Res1999，81，： | 1 |
| 14 | Fatigue cracking resistance of fiber-reinforced asphalt concrete显示文摘 | Lee S J Rust J P Hamouda H | 2005 | Texile Research Journal2005，75，2： | 1 |
| 15 | Sedimentation in an Arctic Lake显示文摘 | Coakley J P Rust B R | 1968 | Journal of Sedimentary Research1968，38，4： | 1 |
| 16 | Influence of bonelead stores on the observed effectiveness of lead hazard intervention 显示文摘 | Rust S W Kumar P Burgoon D A | 1999 | Environmental Research1999，81，： | 1 |
| 17 | Gliomatosis cerbri:pitfalls in diagnosis显示文摘 | Rust P Ashkan K Ball C | 2001 | J Clin Neurosci2001，8，4： | 1 |
| 18 | Complications associated with removal of the laryngeal mask airway:a comparison of removal in deeply anaesthetised versus awake patients显示文摘 | Gataure P S Latto L P Rust S | 1995 | Can J Anaesth1995，42，12： | 1 |
| 19 | A systematic reviewof psychosocial outcomes within 2 years of paediatric traumaticbrain injury in a school-aged population 显示文摘 | TRENCHARD SO RUST S BUNTON P | 2013 | Brain Inj2013，27，11： | 1 |
| 20 | Open data in science 显示文摘 | RUST P M | 2008 | Serials Reviews2008，，1： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员