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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 | Response of endophytic bacterial communities in potato plants to infection with Erwinia carotovora subsp, atroseptica 显示文摘 | Reiter B Pfeifer U Schwab H 2002 | 2002 | Appl Environ Microbiol2002，68，5： | 1 |
| 3 | Cuhivition-independent population analysis of bacterial endophytes in three potato varieties based on eubacterial and Actinomycetes-specific PCR of 16S rRNA genes 显示文摘 | Sessitsch A Reiter B Pfeifer U 2002 | 2002 | FEMS Microbiology Ecology2002，39，： | 1 |
| 4 | Engineering interchain disulfide bonds into conserved framework regions of Fv fragments: improved biochemical characteristics of recombinant immunotoxins containing disulfide-stabilized Fv显示文摘 | Reiter Y Brinkmann U Webber KO | 1994 | Protein Eng1994，7，5： | 1 |
| 5 | Cultivation-independent population analysis of bacterial endophytes in three potato varieties based on eubacterial and actinomycetes-specific PCR of 16S rRNA genes显示文摘 | Sessitsch A Reiter B Pfeifer U | 2002 | FEMS Microbiology Ecology2002，39，： | 1 |
| 6 | Finite element simulation o{ cold isostatic pressing and sintering of SiC components显示文摘 | Reiterer M Kraft T Janosovits U | 2004 | Ceram Int2004，30，2： | 1 |
| 7 | Cultivation- independent population analysis of bacterial endophytes in three potato varieties based on eubacterial and Actinomyeetes-specific PCR of 16S rDNA genes显示文摘 | Sessitsch A Reiter B Pfeifer U | 2002 | FEMS Microbiol Ecol2002，39，： | 1 |
| 8 | Response of endophytic bacterial communities in potato plants to infection with Erwinia carotovora subsp atroseptica显示文摘 | REITER B PFEIFER U SCHWAB H | 2002 | Appl Environ Microbiol2002，68，： | 1 |
| 9 | Cultivation-independent population analysis of bacterial endophytes in three potato varieties based on eubaeterial and Aetinomyeetes-speeifie PCR of 16S rDNA genes显示文摘 | Sessitsch A Reiter B Pfeifer U | 2002 | FEMS Mierobiol Eeol2002，39，： | 1 |
| 10 | Cultivation -independent popu-lation analysis of bacterial endophytes in three potato varieties basedon eubacterial and A ctinomycetes -specific PCR of 16S rRNA genes显示文摘 | Sessitsch A Reiter B Pfeifer U | 2002 | FEMS Microbiology Ecology2002，39，1： | 1 |
| 11 | Cultivation- independent population analysis of bacterial endophytes in three potato varieties based on eubacterial and Actinomyeetes-specific PCR of 16S rDNA genes显示文摘 | Sessitsch A Reiter B Pfeifer U | 2002 | FEMS Microbiol Ecol2002，39，： | 1 |
| 12 | Finite element simulation of cold isostatic pressing and sintering of SiC components显示文摘 | Reiterer M Kraft T Janosovits U | 2004 | Ceramics International2004，30，： | 1 |
| 13 | Cultivation-independent population analysis of bacterial endophytes in three potato varieties based on eubacterial and Actinomycetes-specific PCR of 16S rRNA genes显示文摘 | Sessitsch A Reiter B Pfeifer U | 2002 | FEMS Microbial Ecology2002，39，1： | 1 |
| 14 | Cultivation - independent population analysis of bacterial endophytes in throe potato varieties based on eubacterial and Actinomycetes - specific PCR of 16S rRNA genes 显示文摘 | Sessitsch A Reiter B Pfeifer U | 2002 | FEMS Microbiology Ecology2002，39，1： | 1 |
| 15 | Aurora kinase a messenger RNA overexpression is correlated with tumor progression and shortened survival in head and neck squamous cell carcinoma显示文摘 | Reiter R Gais P Jutting U | 2006 | Clin Cancer Res2006，12，17： | 1 |
| 16 | Engineering antibody Fv fragments for cancer detection and therapy: disulfide-stabilized Fv fragments 显示文摘 | Reiter Y Brinkmann U Lee B | 1996 | Nature Biotech1996，14，10： | 1 |
| 17 | Aurora kinase A messenger RNA overexpression is correlated with tumor progression and shortened survival in head and neck squamous cell carcinoma显示文摘 | Reiter R Gais P Jütting U | 2006 | Clin Cancer Res2006，12，17： | 1 |
| 18 | A recombinant immunotoxin containing a disulfide-stabilized Fv fragment显示文摘 | Brinkmann U Reiter Y Jung SH | 1993 | Proc Natl Acad Sci USA1993，90，16： | 1 |
| 19 | Organ sparing surgery for giant bilateral renal oncocytoma显示文摘 | Ponholzer A Reiter W J Maier U | 2002 | J Urol2002，168，6： | 1 |
| 20 | Signal transduction pathways involved in melatonin-induced neuroprotection after focal cerebral ischemia in mice显示文摘 | Kilic U Kilic E Reiter RJ | | 0，，01： | 1 |
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