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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 | Control of flowering time in temperate cereals : genes, domestication, and sustainable produc- tivity 显示文摘 | Cockram J Jones H Leigh F J | 2007 | J Exp Bot2007，58，6： | 1 |
| 3 | 显示文摘 | Leigh R Parameswaran K | 2000 | Am J Respir Crit Care Med2000，161，21： | 1 |
| 4 | Direct dating of sulfides by Rb-Sr: A critical test using the Polaris Mississippi Valley-type Zn-Pb deposit显示文摘 | 1995b Christensen J N Halliday A N Leigh K E | 1995 | Geochim Cosmochim Acta1995，59，： | 1 |
| 5 | The influence of artificial macropores on water and solute transport in ]aboratory soil co]urnns 显示文摘 | Buttle J M Leigh D G | 1997 | Journal of Hydrology1997，17，： | 1 |
| 6 | Induced spu- tum cell counts in healthy adults显示文摘 | BELDA J LEIGH R PARAMESWARAN K | 2000 | Am J Respir Crit Care Med2000，161，21： | 1 |
| 7 | Half-rotation in a kinetically lockedcatenane induced by transition metal ion substitution显示文摘 | Leigh D A Lusby P J Slawin A M | 2012 | Chem Commun2012，48，47： | 1 |
| 8 | Certification of SRM 1589a PCBs, pesticides, PBDEs, and dioxins/furans in human serum显示文摘 | Schantz M Keller J Leigh S | 2007 | Anal Bioanal Chem2007，389，4： | 1 |
| 9 | Control of flowering time in temperate cereals : genes, domestication, and sustainable produc- tivity显示文摘 | Cockram J Jones H Leigh F J | 2007 | J Exp Bot2007，58，6： | 1 |
| 10 | The exploitation of the genome in the search for determinants of virulence in Streptococcus uberis 显示文摘 | LEIGH J A WARD P N FIELD T R | 2004 | Veterinary Immunology and Immunopathology2004，100，： | 1 |
| 11 | The image invention dur- ing the competitive season with an elite union player显示文摘 | LYNNE E LEIGH J RICHARD M | 2004 | Sport Psychol2004，，8： | 1 |
| 12 | Potential role for a Carbohydrate moiety in anti-candida activity of human oral epithelial cells 显示文摘 | Steele CH Leigh J Swoboda R | 2001 | Infect And Immun2001，69，11： | 1 |
| 13 | Induced sputum cell counts in healthy adults显示文摘 | Belda J Leigh R Parameswaran K | 2000 | Am J Respir Crit Care Med2000，161，2： | 1 |
| 14 | Perfusion imaging 显示文摘 | Detre J A Leigh J S Williams D S et aI | 1992 | Magn Reson Med1992，23，1： | 1 |
| 15 | What is clinical pathway development of a definition to inform the debate显示文摘 | Leigh K Thomas R Erica J | 2010 | BMC Medicine2010，，8： | 1 |
| 16 | Induced sputum cell counts in healthy adults显示文摘 | BELDA J LEIGH R PARAMESWARAN K | 2000 | Am J Respir Crit Care Med2000，161，21： | 1 |
| 17 | Advantages of isothermal titration calorimetry for xylanase kinetics in comparison to chemical-reducing-end assays 显示文摘 | MARTIN J B LEIGH M PETER W | 2011 | Analytical Biochemistry2011，，410： | 1 |
| 18 | Costs differences across demographic groups and types of occupational injuries and illnesses显示文摘 | LEIGH J P WAEHRER C MILLER T R | 2006 | American Journal of Industrial Medicine2006，49，10： | 1 |
| 19 | Induced sputum cell counts in healthy adults显示文摘 | Belda J Leigh 1~ Parameswaran K | 2000 | Am J Respir Crit Care Med2000，161，21： | 1 |
| 20 | Happiness and the human development index: Australia is not a paradox显示文摘 | Leigh A Wolfers J | 2006 | Aust Econ Rev2006，39，2： | 1 |
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