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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 | Classifying intertrochanteric fractures of the proximal femur: Does experience matter 显示文摘 | Fung W Jonsson A Buhren V | 2007 | Med Princ Pract2007,16,3: | 1 |
| 3 | Kinetic analysis of the transformation of phthalic esters in a series of stoichio-metric reactions in anaerobic wastes显示文摘 | Vavilin V A Jonsson S Svensson B H | 2005 | Applied Microbiolo-gy and Biotechnology2005,69,: | 1 |
| 4 | Magnesia-carbonrefractory dissolution in Al-killed low carbon steel显示文摘 | Jansson S Brabie V Jonsson P | 2006 | Ironmaking and Steelmaking2006,33,5: | 1 |
| 5 | The search for putative unifying genetic factors for components of the metabolic syndrome 显示文摘 | Sjogren M Lyssenko V Jonsson A | 2008 | Diabetologia2008,51,12: | 1 |
| 6 | Properties and genetic control of four methyltransferases involved in methylation of anthocyanins in flowers of Petunia hybrida显示文摘 | Jonsson L M V Aarsman M E G Poulton J E | 1984 | Planta1984,160,2: | 1 |
| 7 | Classifying intertrochanteric ractures of the proximal femur:does experience matter显示文摘 | Fung W Jonsson A Buhren V | 2007 | Med Princ Pract2007,16,3: | 1 |
| 8 | Lasting improvement of hyperglycaemia and bodyweight: low-carbohy- drate diet in type 2 diabetes a brief report显示文摘 | NIELSEN J V JONSSON E NILSSON A K | 2005 | Ups Med Sci2005,110,2: | 1 |
| 9 | Experiments on Turbulentflow Phenomena in Eccentric Annular Ducts显示文摘 | Jonsson V K Sparrow E M | | 0,,: | 1 |
| 10 | Clinical risk factors, DNA variants, and the development of type 2 diabetes 显示文摘 | Lyssenko V Jonsson A Almgren P | 2008 | N Engl J Med2008,359,21: | 1 |
| 11 | Clinical risk factors, DNA variants and the development of type 2 diabetes 显示文摘 | Lyssenko V Jonsson A Almgren P | 2008 | N Engl J Med2008,359,: | 1 |
| 12 | Corrosion mechanism of commercial MgO-C refractors in contact with different gas atmospheres 显示文摘 | JANSSON S BRABIE V JONSSON P | 2008 | ISIJ Int2008,48,6: | 1 |
| 13 | Excitonic and recombination process in CaWO4 and CdWO4 scin- tiUators under synchrotron irradition显示文摘 | V Nagirnyi E Feldbach L Jonsson | 1998 | Radiat Meas1998,29,34: | 1 |
| 14 | On the role of non-metallic inclusions in the nucleation of acicular ferrite in steels显示文摘 | SARMA D S KARASEV A V JONSSON P G | 2009 | ISIJ International2009,49,7: | 1 |
| 15 | Testing models fortemperature dependence of the inactivation rate of bacillus spores显示文摘 | Jonsson V Sngag B G | 1997 | Food science1997,42,5: | 1 |
| 16 | Interaetion between prenatal growth and high-risk genotypes in the development of type 2 diabetes显示文摘 | Pulizzi N Lyssenko V Jonsson A | 2009 | Diabetologia2009,52,5: | 1 |
| 17 | Spatial distribution of epiphytes on Populus tremula in relation to dispersal mode显示文摘 | HEDENAS H BOLYUKH V O JONSSON B G | 2003 | Journal of Vegetation Science2003,14,2: | 1 |
| 18 | Fouling of electrodialysis membranes by organic substances显示文摘 | Sundstrom G Jonsson A S | 2000 | Desalination2000,128,: | 1 |
| 19 | Modelling MSW decomposition under landfill conditions considering hydrolytic and methanogenic inhibition 显示文摘 | Vavilin V A Jonsson S Ejlertson J | 2006 | Biodegradafion2006,17,5: | 1 |
| 20 | Lessons from the past: familial aggregation analysis of fatal pandemic influenza (Spanish flu) in Iceland in 1918 显示文摘 | Gottfredsson M Halldorsson B V Jonsson S | 2008 | Proc Natl Acad Sci USA2008,105,4: | 1 |