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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 | Reliability of nominal data based on qualitative judgments显示文摘 | Perreault W D Leigh L E | 1989 | Journal of Marketing Research1989，26，2： | 1 |
| 3 | A robust method for quantification of volatile compounds within and between vintages using headspace-solid-phase micro-extraction coupled with GC-MS:applica-tion on Semillon wines显示文摘 | REBIERE L CLARK A C LEIGH M S | 2010 | Anal Chim Acta2010，660，： | 1 |
| 4 | Molecular characterisation of hepatopancreatic parvovirus (PmergDNV) from Australian Penaeus merguiensis显示文摘 | Kathy A L Jennifer E Leigh O | 2007 | Virology2007，362，： | 1 |
| 5 | Cellulose utilization in forest litter and soil: identification of bacterial and fungal decomposers显示文摘 | Stursov~i M if6tkovi L Leigh BM | 2012 | FEMS Microbiology Ecology2012，80，3： | 1 |
| 6 | Physician career satisfaction across specialties显示文摘 | J Paul Leigh Richard L Kravitz Mike Schembri | 2002 | Archives of Internal Medicine2002，162，14： | 1 |
| 7 | Quantifying arbitrary magnetic susceptibility distributions with MR显示文摘 | Li L Leigh J S | 2004 | Magn Reson Med2004，51，5： | 1 |
| 8 | Alfalfa harvest strategy effect on Lygus bug ( I-Iemiptera: Miridae) and insect predator population density :Implications for use as trap crop in cotton 显示文摘 | GODFREY L D LEIGH T F | 1994 | Environmental entomology1994，23，： | 1 |
| 9 | Reliability of Nominal Data Based on Qualitative Judgments显示文摘 | PERREAULT W LEIGH L | 1989 | Journal of Marketing Research1989，26，5： | 1 |
| 10 | Amyotrophic lateral sclerosis/Riluzole study group Ⅱ 显示文摘 | Lacomblez L Bensimon G Leigh PN : Dose-ranging study of riluzole in amyotrophic lateral sclerosis | 1996 | Lancet1996，347，： | 1 |
| 11 | Dose-ranging study of riluzole in amyotrophic lateral sclerosis显示文摘 | Lacomblez L Bensimon G Leigh P N | 1996 | Lancet1996，347，9013： | 1 |
| 12 | Non-planar co-ordination of the Schiffbasedianion N,N'-2,2 dimethyltrimethylenebis[salicylideneiminate (2-)]to vanadium显示文摘 | FAIRHURST S A HUGHES D L KLEINKES U LEIGH G J SANDERS J R WEISNER J | | 0，，03： | 1 |
| 13 | Physician Career Satisfaction Across Specialties 显示文摘 | J Paul Leigh Richard L Kravitz Mike Schembri | 2002 | Archives of Internal Medicine2002，162，： | 1 |
| 14 | Dynamic characterizatioon of an inflatable concentrator for solar thermal propulsion显示文摘 | Larry M Leigh Michael L Tinker | 2003 | Journal of spacecraft and rockets2003，40，1： | 1 |
| 15 | Dynamic characterization of an inflatable concentrator for solar thermal propulsion显示文摘 | Larry M Leigh Michael L Tinker | 2003 | Journal of Spacecraft and Rockets2003，40，1： | 1 |
| 16 | Association of pl6INK4a overexpression with improved outcomes in young pa- tients with squamous cell cancers of the oral tongue 显示文摘 | Stephen L Harris Leigh B Thorne William T Seaman | 2010 | Wiley Online Library2010，5，： | 1 |
| 17 | Metallothionein isoform expression by breast cancer cells显示文摘 | Natalie L Barnes M Leigh A | 2000 | Int J Biochem & Cell Biol2000，32，： | 1 |
| 18 | Dynamic Characterization of an Inflatable Concentrator for Solar Thermal Propulsion显示文摘 | Larry M Leigh Michael L Tinker | 2003 | Journal of Spacecraft and Rockets2003，40，1： | 1 |
| 19 | Early reconstitution of immunity and decreased severity of herpes zoster in bone marrow transplant recipients immunized with inactivated varicella vaccine 显示文摘 | Rebecca L R Sonia N Leigh Z | 1997 | J Infect Dis1997，176，： | 1 |
| 20 | Competency assessment models显示文摘 | Leigh I W Smith I L Bebeau M J | 2007 | Prof Psychol-Res Pract2007，38，5： | 1 |
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