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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 | Changes in rain forest tree diversity,dominance and rarity across a seasonality gradient in the Western Ghats,India显示文摘 | Davidar P Puyravaud JP Leigh Jr EG | | 0,,: | 1 |
| 3 | 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 |
| 4 | Adherence to NICE guidance on glucagon-like peptide-1 receptor agonists among patients with type 2 diabetes mellitus:an evaluation using the Clinical Practice Research Datalink显示文摘 | Jameson K D'Oca K Leigh P | 2016 | Curr Med Res Opin2016,32,1: | 1 |
| 5 | 显示文摘 | Leigh R Horsewood P | 2000 | J Allergy Clin Immunol2000,105,61: | 1 |
| 6 | 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 |
| 7 | A new look at psychological climate and its relationship to job involvement, effort, and performance显示文摘 | Brown S P Leigh T W | 1996 | Journal of Applied Psychology1996,81,4: | 1 |
| 8 | 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 |
| 9 | Excitation- emission matrix fluorescence spectroscopy for natural organic matter characterization: A quantitative evaluation of calibration and spectral correction procedures 显示文摘 | Holbrook R D Derose P C Leigh S D | 2006 | Appl Spectrosc2006,60,: | 1 |
| 10 | Epithelial expressionof profibrotic mediators in a model of allergen-induced airwayremodeling显示文摘 | KellyMM Leigh R Bonniaud P | 2005 | Am J Respir Cell Mol Biol2005,32,2: | 1 |
| 11 | GeoWall:Stereoscopic visualization for geoscience research and education显示文摘 | JOHNSON A LEIGH J MORIN P | 2006 | IEEE Computer Graphics and Applications2006,26,6: | 1 |
| 12 | Development of a Multilocus sequence typing scheme for the pig pathogen Streptococcus suis: Identification of virulent clones and potential capsular serotype exchange 显示文摘 | KING S J LEIGH JA HEATH P J | 2002 | Journal of Clinical Microbiology2002,40,10: | 1 |
| 13 | Sputum induction for diagnosis of Pneumocystis carinii pneumonia显示文摘 | Leigh TR Parsons P Hume C | 1989 | Lancet1989,2,8656: | 1 |
| 14 | 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 |
| 15 | High-resolution CT of patients with primary ciliary dyskinesia显示文摘 | Kennedy M P Noone P G Leigh M W | 2007 | AJR2007,188,7: | 1 |
| 16 | High-resolusion CT of patients with primary ciliary dys- kinesia显示文摘 | KENNEDY M P NEONE P G LEIGH M W | 2007 | Am J Roentgenol2007,188,: | 1 |
| 17 | The relation of attachment status, psychiatric classification, and response of psychotherapy显示文摘 | Fonagy P Leigh T Steele M | 1996 | Journal of Consulting and Clinlcal Psychology1996,64,1: | 1 |
| 18 | Predation on spider mite eggs by the western flower thrips,Frankliniella occidentalis(Thysanoptera:Thripidae),an opportunity in a cotton agroecosystem显示文摘 | Trichilo P J Leigh T F | 1986 | Environmental Entomology1986,15,4: | 1 |
| 19 | Influence of resource quality on the reproductive fitness of flower thrips(Thysanoptera,Thripidae),an opportunist in a cotton agroecosystem显示文摘 | Trichilo P J Leigh T F | 1988 | Environmental Entomology1988,15,: | 1 |
| 20 | Costs of needle stick inju- ries and subsequent hepatitis and HIV infection 显示文摘 | Leigh JP Gillen M Franks P | 2007 | Curt Meal Res Opin2007,23,9: | 1 |