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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 | Powder compaction modelling via the discrete and finite element method显示文摘 | Gethin D T Khoei A R | 2000 | Materials and Design2000，21，： | 1 |
| 3 | Numerical comparison of a deformable discrete element model and an equivalent continuum analysis for the compaction of ductile porous material显示文摘 | Ransing R S Lewis R W | 2001 | Computers and Structures2001，79，： | 1 |
| 4 | Computer-aided simulation of metal powder die compaction processes显示文摘 | Lewis R W Jinka A G K Gethin D T | 1993 | Powder Metallurgy1993，25，6： | 1 |
| 5 | Discovery of a high modecular weight complex of calcium,phosphate,fetuin,and matrix-carboxyglutamic acid protei in the serum of etidronatereated rats显示文摘 | Paul A Gethin R Aaron W | 2002 | J Biol Chem2002，277，6： | 1 |
| 6 | An investigation of powder compaction processes显示文摘 | GETHIN D T TRAN D V LEWIS R W | 1994 | Journal of Powder Metallury1994，，30： | 1 |
| 7 | An investigation of powder compaction process显示文摘 | Gethin D T Tran V D Lewis R W | 1994 | International Journal of Powder Metallurgy1994，30，4： | 1 |
| 8 | Powder Compaction Modelling Via the Discrete and Finite Element Method显示文摘 | Ransingu R S Gethin D T Khoei A R P Mosbah R W Lewis | 2000 | Materials and Design2000，21，4： | 1 |
| 9 | Powder Compaction Modelling via the Discrete and Finite Element Method显示文摘 | Ransing R S Gethin D T Khoei A R | 2000 | Mater Design2000，21，： | 1 |
| 10 | An investigation of powder compaction processes显示文摘 | D T Gethin V D Tran R W Lewis | | 0，，： | 1 |
| 11 | Powder compaction modelling via the discrete and finite element method显示文摘 | RANSING R S GETHIN D T KHOEI A R | 2000 | Materials and Design2000，21，： | 1 |
| 12 | Design element con- cept of squeeze casting process 显示文摘 | Ahmad R Gethin D T Lewis R W | 2012 | Applied Mathemati- cal Modeling2012，36，10： | 1 |
| 13 | Computer-aided simulation of metal powder die compaction processes 显示文摘 | LEWIS R W JINKA A G K GETHIN D T | 1993 | Int J Powder Metall1993，25，6： | 1 |
| 14 | An investigation of powder compaction processes 显示文摘 | GETHIN D T TRAN V D LEWIS R W ARIFFIN A K | 1994 | Int J Powder Metall1994，30，4： | 1 |
| 15 | Integrating a global positioning system and accelerometers to monitor the deflection of bridges显示文摘 | Gethin W R Meng Xiaolin Alan H D | | 0，，02： | 1 |
| 16 | Powder compaction modeling via the discrete and finite element method显示文摘 | RANSING R S GETHIN D T KHOEI A R | 2000 | Materials and Design2000，21，： | 1 |
| 17 | An investigation of powder compaction process 显示文摘 | Tran V D Lewis R W | 1994 | International Journal of Powder Metallurgy1994，30，4： | 1 |
| 18 | Measurement of Young's modulus and tensile failure properties of green powder compacts 显示文摘 | KORACHK1N D GETHIN D T LEWIS R W | 2008 | Powder Metallurgy2008，51，2： | 1 |
| 19 | The role of self-blame and worthlessness in the psychopathology of major depressive disorder 显示文摘 | ZAHN R LYTHE KE GETHIN JA | 2015 | J Affect Disord2015，186，： | 1 |
| 20 | Computer-Aided Simulation of Metal Powder Die Compaction Processes 显示文摘 | Lewis R W Jinka A G K Gethin D T | 1993 | Powder Metallurgy Int1993，25，6： | 1 |
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