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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 | 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 |
| 3 | 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 |
| 4 | 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 |
| 5 | 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 |
| 6 | Candidasepecific systemic cell-mediated immune reactivities in human immunodeficiency virus-positive persons with mucosal candidiasis 显示文摘 | Janet E Leigh Melissa Barousse Rolf K | 2001 | The Journal of Infectious Diseases2001,15,: | 1 |
| 7 | Direct dating ofsulfides by Rb-Sr:A critical test using the Polaris Mississippi Val-ley-type Zn-Pb deposit显示文摘 | Christensen J N Halliday A N Leigh K E | 1995 | Geochimica et Cosmochimica Acta1995,59,24: | 1 |
| 8 | GIS-based management system for irrigation districts,In challenges facing irrigation and drainage in the new millennium显示文摘 | Fipps G Leigh E | 2000 | Proceedings US Committee on Irrigation and Drainage Fort Collins Colorado2000,,6: | 1 |
| 9 | Methods of sputum processing for cell counts,immunocytochemistry and in situ hybridisation显示文摘 | Pizzichini E Pizzichini MM Leigh R | 2002 | Eur Respir J Suppl2002,37,: | 1 |
| 10 | Quantitation of time-and frequency-resolved optical spectra for the determination of tissue oxygenation 显示文摘 | SEVICK E M CHANCE B LEIGH J | 1991 | Analytical Biochemistry1991,,: | 1 |
| 11 | Low-density lipoprotein re- ceptor gene familial hypercholesterolemia variant database: update and pathological assessment显示文摘 | Usifo E Leigh SE Whittall RA | 2012 | Ann Hum Genet2012,76,5: | 1 |
| 12 | Solitary Extramedullary Plasmacytoma Five Years after Successful Cardiac Transplantation: Case Report and Review of the Literature American 显示文摘 | Leigh B R Larkin E C Scotte D R | 1997 | J Cain Oncology1997,20,: | 1 |
| 13 | Use of a commercial reagent leads to reduced germ tube production by Candida dubliniensis显示文摘 | Leigh E Christine ES William GM | 2005 | J Clin Microbio2005,43,5: | 1 |
| 14 | Induced sputum, eosinophilic bronchitis, and chronic obstructive pulmonary disease 显示文摘 | HARGREAVE F E LEIGH R | 1999 | Am J Respir Crit Care Med1999,160,52: | 1 |
| 15 | Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case–control studies显示文摘 | Celeste Leigh Pearce Claire Templeman Mary Anne Rossing Alice Lee Aimee M Near Penelope M Webb Christina M Nagle Jennifer A Doherty Kara L Cushing-Haugen Kristine G Wicklund Jenny Chang-Claude Rebecca Hein Galina Lurie Lynne R Wilkens Michael E Carney Mar | 2012 | Lancet Oncology2012,,: | 1 |
| 16 | Low-density lipoprotein receptor gene familial hypercholesterolemia variant database: update and pathological assessment 显示文摘 | Usifo E Leigh S E A Whittall R A | 2012 | Annals of Human Genetics2012,76,5: | 1 |
| 17 | Systematic analysis of bacterialeffectorpostsynaptic density 95/disc large/zonula occludens-1(PDZ)domain interactions demonstrates Shigella Osp E proteinpromotes protein kinase C activation via PDLIM proteins显示文摘 | Chae-ryun Yi John E Allen Brian Russo Soo Young Lee Jason E Heindl Leigh A Baxt Bobby Brooke Herrera Emily Kahoud Gavin Mac Beath Marcia B Goldberg | 2014 | The Journal of biological chemistry2014,289,30: | 1 |
| 18 | Biphenyl-utilizing bacteria and their functional genes in a pine root zone contaminated with polychlorinated biphenyls (PCBs) 显示文摘 | LEIGH M B PELLIZARI V H UHLIK O SUTKA R RODRIGUES J OSTROM N E ZHOU J IEDJE J M | 2007 | ISME J2007,1,13: | 1 |
| 19 | The diagnosis of Huntington's disease 显示文摘 | Folstein S E Leigh R J Parhad I M | 1986 | Neurology1986,36,10: | 1 |
| 20 | A new approach to measuring socially responsible consumption tendencies 显示文摘 | LEIGH J H MURPHY P E ENIS B M | 1988 | Journal of Macro marketing1988,8,: | 1 |