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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 | Field demonstration of in situ immobilization of soil Pb using P amendments显示文摘 | Ming Chen Lena Q Ma Satya P Singh Rocky X Cao Ricardo Melamed | 2002 | Advances in Environmental Research2002，，1： | 2 |
| 3 | Fast-track anesthesia with remifentanil and spinal analgesia for surgery: the effect on pain control and quality of reeovery显示文摘 | Lena P Balarac N Lena D | 2008 | J Cardiothorac Vasc Anesth2008，22，4： | 1 |
| 4 | Structure and function of buffer strips from a water quality perspective in agriculture landscapes显示文摘 | Lena B-M Gilles P Ann F | 1995 | Landscape Urban Plan1995，31，： | 1 |
| 5 | Coimmunization of rhesus macaques with plasmid vectors expressing IFN-g, GM-CSF, and SIV antigens enhances anti-viral humoral immunity but does not affect viremia after challenge with highly pathogenic virus显示文摘 | LENA P VILLINGER F GIAVEDONI L | 2002 | Vaccine2002，20，4： | 1 |
| 6 | miR-203 represses 'sternness' by repressing DeltaNp63 显示文摘 | A M Lena R Shalom-Feuerstein P Rivetti di Val Cervo | 2008 | Cell Death Differ2008，15，7： | 1 |
| 7 | Structure and function of buffer strip s from a water quality perspective in agriculture landscapes显示文摘 | Lena B M Gilles P Ann F | 1995 | Landscape and Urban Planning1995，31，： | 1 |
| 8 | miR- 203 represses 'sternness' by repressing DehaNp63 显示文摘 | Lena AM Shalom-Feuerstein R Rivetti di Val Cervo P | 2008 | Cell Death Differ2008，15，7： | 1 |
| 9 | Evaluation of 138 fractures of the cervical spine during a recent 5 - year- period( 1979-983 ) : therapentic approaches显示文摘 | Reynier Y Lena G Vazqnez P | 1985 | Nearo - chirargic1985，31，2： | 1 |
| 10 | p63-microRNA feed- back in keratinocyte senescence显示文摘 | Rivetti di Val Cervo P Lena AM Nieoloso M | 2012 | Proc Natl Acad Sci USA2012，109，4： | 1 |
| 11 | Changing landscape of hepatitis C virus-positive donors显示文摘With the introduction of the new highly effective antiviral therapies, there has been a dramatic increase in the use of the hepatitis C virus(HCV)-positive livers in HCV-positive recipients. In the majority of studies, HCV positivity was defined as a donor testing HCV Ab positive. In 2015, all Organ Procurement Organizations were mandated to perform and report HCV Nucleic Acid Amplification Testing(NAT) results on all deceased and living donors. Studies are not yet available on how organs are being utilized based on NAT status and whether NAT status affects recipient outcomes. Further studies are needed to maximize the use of these organs. | Catherine E Kling Ajit P Limaye Lena Sibulesky | 2017 | World Journal of Hepatology2017，9，20： | 1 |
| 12 | miR-203 represses 'sternness'by repressing DehaNp63显示文摘 | Lena AM Shalom-Feuerstein R Rivetti di Val Cervo P | 2008 | Cell Death Differ2008，15，7： | 1 |
| 13 | Astmphsical results with the Comeon Adaptive Optics System 显示文摘 | Lena P J | 1994 | Proc SPIE1994，22，1： | 1 |
| 14 | Field demonstration of in situ immobilization of soil Pb using P amendments显示文摘 | Ming Chen Lena Q Ma Satya P Singh | 2003 | Advances in Environmental Research2003，8，1： | 1 |
| 15 | Coexistence of three competing microbial populations in a chemostat with periodically varying dilution rate显示文摘 | Lenas P Pavlou S | 1995 | Math Biosci1995，129，： | 1 |
| 16 | Coexistence of three competing microbial populations in a chemostat with periodically varying dilution rate 显示文摘 | Lenas P Pavlous S | 1995 | Math Biosci1995，129，： | 1 |
| 17 | MicroRNA - 191 triggers keratinoeytes senescence by SATB1 and CDK6 downregulation 显示文摘 | Lena AM Mancini M Rivetti di Val Cervo P | 2012 | Biochem Biophys Res Commun2012，423，3： | 1 |
| 18 | Structure and function of buffer strip s from a water quality perspective in agriculture landscapes 显示文摘 | Lena B M Gilles P Ann F | 1995 | Landscape and Urban Planning1995，31，13： | 1 |
| 19 | Mi- croRNA-191 triggers keratinocytes senescence by SATB1 and CDK6 downregulation显示文摘 | Lena AM Mancini M Rivetti di Val Cervo P | 2012 | Biochem Biophys Res Commun2012，423，3： | 1 |
| 20 | Adsorption of chromium (VI) ion from aqueous solution by succinylated mercerized cellulose functionalized with quaternary ammonium groups显示文摘 | Gurgel L V A de Melo J C P de Lena J C | 2009 | Bioresource Technology2009，100，13： | 1 |
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