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| 1 | Anti-inflammatory effects of bifidobacteria by inhibition of LPS-induced NF-κB activation显示文摘AIM: Different strains of bifidobacteria were analysed for their effects on HT-29 intestinal epithelial cells (IECs) in in vitro models both of the non-inflamed and inflamed intestinal epithelium. METHODS: A reporter gene system in HT-29 cells was used to measure levels of NF-KB activation after challenge with bifidobacteria or after bacterial pre-treatment following LPS challenge. IL-8 protein and pro-inflammatory gene expression was investigated using normal HT-29 cells. RESULTS: None of the bifidobacteria tested induced activation of nuclear factor KB (NF-KB) indicating that bifidobacteria themselves do not induce inflammatory events in IECs. However, six out of eight bifidobacteria tested inhibited lipopolysaccharide- (LPS-) induced NFKB activation in a dose- and strain-dependent manner. In contrast, NF-KB activation in response to challenge with tumor necrosis factor-α(TNF-α) was affected by none of the tested bifidobacteria, indicating that the inhibitory effect of bifidobacteria is specific for LPS-induced inflammation in IECs. As shown with two of the six inhibitionpositive bifidobacteria, LPS-induced inhibition of NFKB activation was accompanied by a dose-dependent decrease of interleukin 8 (IL-8) secretion and by lower mRNA levels for IL-8, TNF-a, cyclooxygenase 2 (Cox-2), and intercellular adhesion molecule 1 (ICAM-1). CONCLUSION: Some strains of bifidobacteria are effective in inhibiting LPS-induced inflammation and thus might be appropriate candidates for probiotic intervention in chronic intestinal inflammation. | Christian U Riedel Francis Foata David Philippe Oskar Adolfsson Bernhard J Eikmanns Stephanie Blum | 2006 | World Journal of Gastroenterology2006，12，23： | 14 |
| 2 | 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 |
| 3 | The β-lactam antibiotic, ceftriaxone, dramatically improves survival, increases glutamate uptake and induces neurotrophins in stroke显示文摘 | Christa Th?ne-Reineke Christian Neumann Pawel Namsolleck Kristin Schmerbach Maxim Krikov Jan H Schefe Kristin Lucht Heide H?rtnagl Michael Godes Susanne Müller Kay Rumschüssel Heiko Funke-Kaiser Arno Villringer U Muscha Steckelings Thomas Unger | 2008 | Journal of Hypertension2008，，12： | 2 |
| 4 | Toxicodynamic therapeutic drug monitoring of immunosuppressants: promises, reality, and challenges显示文摘 | Christians U Schmitz V Schoning W | 2008 | Ther Drug Monit2008，30，2： | 1 |
| 5 | Simplified highperformance liquid chromatograph-mass spectrometry assay for measurement of tacrolimus and its metabolites and cross validation with microparticle enzyme immunoassay 显示文摘 | Gobschior AK Christians U Winkler M | 1995 | Ther Drug Moni1995，17，： | 1 |
| 6 | Grapefurit juice activates P-glycoprotein-mediated drug transport 显示文摘 | Soldner A Christians U Susanto M | 1999 | Pharm Res1999，16，： | 1 |
| 7 | Mechanism of clinically relevant drug interactionsassociated with Ta- crolimus显示文摘 | Christians U Jacobsen W Benet LZ | 2002 | Clin Pharmacokinet2002，41，11： | 1 |
| 8 | Cardiac resynchronization therapy improves central sleep apnea and Cheyne-Stokes respiration in patients with chronic heart failure显示文摘 | Anil-Martin Sinha Erik C Skobel Ole-Alexander Breithardt Christine Norra Kai U Markus Christian Breuer Peter Hanrath Christoph Stellbrink | 2004 | Journal of the American College of Cardiology2004，，1： | 1 |
| 9 | CYP3A4- transfected Caco-2 cells as a tool for understanding bioohemical ab- sorption barriers: studies with sirollmus and midazolam显示文摘 | CUMMINs C L JACOBSEN W CHRISTIANS U | 2004 | J Phar- macol Exper Ther2004，308，1： | 1 |
| 10 | Pitfalls in monitoring tacrolimus (FK506) 显示文摘 | Braun F Schutz E Christians U | 1997 | Ther Drug Moni1997，19，： | 1 |
| 11 | Grapefruit juice activates P-glycoproteinmediated drug transport显示文摘 | Soldner A Christians U | 1999 | Pharm- Res1999，16，4： | 1 |
| 12 | Improvements of AE technique using wavelet algorithms,coherence functions and automatic data analysis显示文摘 | Christian U Grosse Florian Finck Jochen H Kurz | 2004 | Construction and Building Materials2004，18，： | 1 |
| 13 | Mechanism of c-linically relevant drug interactions associated with Tacrolimus显示文摘 | Christians U Jacobsen W Benet L Z | 2002 | Clin Pharmacokinet2002，41，11： | 1 |
| 14 | The sialomucin CD34 is amarker of lymphatic endothelial cells in human tumors显示文摘 | Fiedler U Christian S Koidl S | 2006 | Am JPathol2006，168，3： | 1 |
| 15 | Discovery of potent and selective agonists forthe freefatty acid receptor 1 ( FFA1/GPR40),a potential target for thetreatment of type II diabetes显示文摘 | Elisabeth C Christian U | 2008 | Journal of Medicinal Chemistry2008，51，22： | 1 |
| 16 | Human cytomegalovirus prevents replication licensing by inhibiting MCM loading onto chromatin 显示文摘 | Luder W Ralf U Christian H | 2003 | EMBO reports2003，4，1： | 1 |
| 17 | The membrane form of the type Ⅱ IL-1 receptor accounts for inhibitory function显示文摘 | Detlef N Christian K Michael U | 2000 | J Immunol2000，165，6： | 1 |
| 18 | Identification of a Thymidylate Synthase Gene within the Genome of Chilo Iridescent Virus 显示文摘 | Christian A Tidona U | 1998 | Virus Genes1998，17，3： | 1 |
| 19 | Transient knockout of photosynthesis mediated by electrical signals 显示文摘 | Christiane K Grams T E E Schreiber U | 2003 | New Phytologist2003，161，3： | 1 |
| 20 | Human cytomegalovirus prevents replication licensing by inhibiting MCM loading onto chromation显示文摘 | Lüder W Ralf U Christian H | 2003 | EMBO Reports2003，4，1： | 1 |
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