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| 1 | Macrophage secretory products induce an inflammatory phenotype in hepatocytes显示文摘AIM:To investigate the influence of macrophages on hepatocyte phenotype and function.METHODS:Macrophages were differentiated from THP-1 monocytes via phorbol myristate acetate stimulation and the effects of monocyte or macrophageconditioned medium on HepG2 mRNA and protein expression determined.The in vivo relevance of these findings was confirmed using liver biopsies from 147 patients with hepatitis C virus(HCV)infection.RESULTS:Conditioned media from macrophages,but not monocytes,induced a transient morphological change in hepatocytes associated with upregulation of vimentin(7.8±2.5-fold,P=0.045)and transforming growth factor(TGF)-β1(2.6±0.2-fold,P<0.001)and downregulation of epithelial cadherin(1.7±0.02-fold,P=0.017)mRNA expression.Microarray analysis revealed significant upregulation of lipocalin-2(17-fold,P <0.001)and pathways associated with inflammation,and substantial downregulation of pathways related to hepatocyte function.In patients with chronic HCV,realtime polymerase chain reaction and immunohistochemistry confirmed an increase in lipocalin-2 mRNA(F0 1.0 ±0.3,F1 2.2±0.2,F2 3.0±9.3,F3/4 4.0±0.8,P= 0.003)and protein expression(F1 1.0±0.5,F2 1.3± 0.4,F3/4 3.6±0.4,P=0.014)with increasing liver injury.High performance liquid chromatography-tandem mass spectrometry analysis identified elevated levels of matrix metalloproteinase(MMP)-9 in macrophageconditioned medium,and a chemical inhibitor of MMP-9 attenuated the change in morphology and mRNA expression of TGF-β1(2.9±0.2 vs 1.04±0.1,P<0.001) in macrophage-conditioned media treated HepG2 cells.In patients with chronic HCV infection,hepatic mRNA expression of CD163(F0 1.0±0.2,F1/2 2.8±0.3,F3/4 5.3±1.0,P=0.001)and MMP-9(F0 1.0±0.4,F1/2 2.8±0.3,F3/4 4.1±0.8,P=0.011)was significantly associated with increasing stage of fibrosis.CONCLUSION:Secreted macrophage products alter the phenotype and function of hepatocytes,with increased expression of inflammatory mediators,suggesting that hepatocytes actively participate in liver injury. | Michelle Melino Victoria L Gadd Gene V Walker Richard Skoien Helen D Barrie Dinesh Jothimani Leigh Horsfall Alun Jones Matthew J Sweet Gethin P Thomas Andrew D Clouston Julie R Jonsson Elizabeth E Powell | 2012 | World Journal of Gastroenterology2012,18,15: | 3 |
| 2 | Inorganic -organic hybrids by exfoliation of MoS2 显示文摘 | Powell A V Kosidowski L McDowall A | 2001 | Journal of Materials Chemistry2001,11,: | 1 |
| 3 | A rapid technique for the isolation and purification of adult cardiac muscle cells having respiratory control and a tolerance to calcium 显示文摘 | Powell T Twist V W | 1976 | Biochem Biophys Res Commun1976,72,: | 1 |
| 4 | Expression of snowdrop lectin in transgenic tobacco plants results in added protectin against aphids 显示文摘 | HILDER V A POWELL K S GATEHOUSE A M R | 1995 | Transgenic Research1995,4,: | 1 |
| 5 | Effect of elevated CO2 on photosynthesis,respiration and growth of perennial ryegrass显示文摘 | RYLE G J A POWELL C E TEUSON V | | 0,,: | 1 |
| 6 | Caries risk assessment:relevance to the practitioner显示文摘 | Powell L V | 1998 | J Am Dent Assoc1998,129,3: | 1 |
| 7 | A Method for Assessing Hydrologic Alteration within Ecosystems显示文摘 | Richter B D Baumgartner J V Powell J | 1996 | Conservation Biology1996,10,4: | 1 |
| 8 | Preen gland function in layer fowls: factors affecting morphology and feather lipid levels显示文摘 | Sandilands V Savory J Powell K | 2004 | Comp Biochem Physiol A Mol Integr Physiol2004,137,1: | 1 |
| 9 | Preen gland function in layer fowls: factors affecting preen oil fatty acid composition显示文摘 | Sandilands V Powell K Keeling L | 2004 | Br Poult Sci2004,45,1: | 1 |
| 10 | Assessing representativeness of the protected natural areas in Costa Rica for conserving biodiversity: A preliminary gap analysis 显示文摘 | Powell G V N Barborak J Rodriguez M | 2000 | Biological Conservation2000,93,: | 1 |
| 11 | Assessing representativeness of protected natural areas in Costa Rica for protecting biodiversity:A preliminary gab analysis显示文摘 | Powell G V N Barborak J Rodriguez M | 2000 | Biological Conservation2000,93,: | 1 |
| 12 | Antimetabolic effects of plant lectins and plant and fungal enzymes on the nymphal stages of two important rice pests,Nilaparvata Lugens and Nephotettix Cinciteps显示文摘 | Powell K S Gathouse A M R Hilder V A | 1993 | Entomal Exp Appl1993,66,2: | 1 |
| 13 | Expression of snow drop lectin in transgenic tobacco plants results in added protection against aphids显示文摘 | Hilder V A Powell K S Gatehouse A M R | 1995 | Transgenic Reseach1995,4,: | 1 |
| 14 | Interleukin-10 Gene Expression in Acute Virus-induced Asthma显示文摘 | Grissell T V Powell H Darren R | 2005 | Am J Respir Crit Care Med2005,172,: | 1 |
| 15 | A method for assessing hydrologic alteration within ecosystems 显示文摘 | Richter B D Baumgartner J V Powell J | 1996 | Conservation Biology1996,10,4: | 1 |
| 16 | Analysis of multi-component evaporation in electron beam melting and refining of titanium alloys显示文摘 | POWELL A AVYLE J V D | 1997 | Metallurgical Materials Transactions1997,28,: | 1 |
| 17 | Antifeedant effects of plant lectins and an enzyme on the adult stages of the rice brown planthopper,Nilaparvata Lugens显示文摘 | Powell K S Gathouse A M R Hilder V A | 1995 | Entomal Exp Appl1995,75,1: | 1 |
| 18 | Gender and DSS design: The research implications 显示文摘 | Powell P L Johnson J E V | 1995 | Decision SupportSystems1995,14,1: | 1 |
| 19 | A method for assessing hydrologic alteration within ecosystems 显示文摘 | Richter B D Baumgartner J V Powell J | 1996 | Conservation Biology1996,10,4: | 1 |
| 20 | Expression of snowdrop lectin in transgenic tobacco plants in added protection against aphids显示文摘 | Hilder V A Powell K S Gathouse A M R | 1995 | Transgenic Res1995,4,1: | 1 |