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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 | Assimilation of remotely sensed data for improved latent and sensible heat flux prediction: A comparative synthetic study 显示文摘 | Pipunic R C Walker J P Western A | 2008 | Remote Sensing of Environ- ment2008，112，4： | 1 |
| 3 | Biological invasion by Myricafaya in Hawai'i: plant demography, nitrogen fixation, ecosystem effects显示文摘 | VITOUSEK P M WALKER L R | 1989 | Ecological Monographs1989，59，： | 1 |
| 4 | Competency assessment: methods for development and implementation in nursing education 显示文摘 | Redman R W Lenburg C B Hinton Walker P | 1999 | Online Journal of Issues in Nursing1999，4，2： | 1 |
| 5 | Adaptation of HIV-1to human leukocyte antigen class I显示文摘 | Kawashima Y Pfafferott K Frater J Matthews P Payne R Addo M Gatanaga H Fujiwara M Hachiya A Koizumi H Kuse N Oka S Duda A Prendergast A Crawford H Leslie A Brumme Z Brumme C Allen T Brander C Kaslow R Tang J Hunter E Allen S Mulenga J Branch S Roach T John M Mallal S Ogwu A Shapiro R Prado J G Fidler S Weber J Pybus O G Klenerman P Ndung'u T Phillips R Heckerman D Harrigan P R Walker B D Takiguchi M Goulder P | 2009 | Nature2009，458，7238： | 1 |
| 6 | One-dimensional soil moisture profile retrieval by assimilation of near-surface observations: a comparison of retrieval algorithms显示文摘 | Walker J P Willgoose G R Kalma J D | 2001 | Advances in Water Resources2001，24，： | 1 |
| 7 | Variations in stream water uptake by Eucalyptus camaldulensis with differing access to stream water 显示文摘 | Thorbum P J Walker G R | 1994 | Oecologia1994，100，： | 1 |
| 8 | Cascaded DC-DC converter connection ofphotovoltaic modules显示文摘 | Walker G R Semia P C | 2004 | IEEE Transactions on Power Electronics2004，19，4： | 1 |
| 9 | Splenic T lympho- cytes die preferentially during heat-induced apoptosis: NuMA reorganization as a marker显示文摘 | Sodja C Brown D L Walker P R | 1998 | Journal of cell science1998，111，16： | 1 |
| 10 | New TechnologiesRequire Advances in Hydrologic Data Assimilation显示文摘 | Walker J P Houser P R Reichle R | 2003 | EOS2003，84，： | 1 |
| 11 | An assess-ment of pollution impacts due to the oil and gas industries in the Pechora basin,north-eastern European Russia显示文摘 | WALKER T R CRITTENDEN P D YOUNG S D | 2006 | Ecological Indicators2006，6，2： | 1 |
| 12 | Biological invasion by myrica-faya in hawaii - plant demography, nitrogenfixation, ecosystem effects显示文摘 | Vitousek P M Walker L R | 1989 | Ecological Monographs1989，59，3： | 1 |
| 13 | The synthesis and antiviral properties of E-5- (2-bromovinyl) -4'-thio-deoxyurichine 显示文摘 | Dyson M R Coe P L Walker R T | 1991 | J Chem Soc Chem Commun1991，，： | 1 |
| 14 | Metalorganic Chemical Vapor Deposition of Monocrystalline GaN Thin Films on β-LiGaO2 substrates显示文摘 | Kung P Saxler A Zhang X Walker D Lavado R Razeghi M | 1996 | Applied Physics Letters1996，69，14： | 1 |
| 15 | Diagnosis and management of spontaneoustramsmural rapture of the esophagus显示文摘 | WALKER W S CAMERON E W J WALBAUM P R | 1985 | Br J surg1985，72，： | 1 |
| 16 | Extended versus ensemble filtering for land data assimilation显示文摘 | Reichle R H Walker J P Koster R D | 2002 | Journal of Hydrometeorology2002，3，12： | 1 |
| 17 | The shape of large surface waves on the open sea and te Draupner New Year wave显示文摘 | Walker DAG Taylor P H Eatock R Taylor | 2004 | Applied Ocean Research2004，26，： | 1 |
| 18 | Interactions between oestradiol and glucocorticoid regulatoryeffects on liver-specific glucocorticoid-inducible genes : possibleevidence for a role of hepatic 1 l(3-hydroxysteroid dehydrogenasetype 1 显示文摘 | JAMIESON P M NYIRENDA M J WALKER B R | 1999 | J Endocrinol1999，160，1： | 1 |
| 19 | Priodic magnets for free electron lasers显示文摘 | | 1985 | Nucl Instr and1985，237，： | 1 |
| 20 | Role of nitric oxide in lipopolysaccharide-induced oxidant stress in the rat kidney显示文摘 | Zhang C Walker L M Mayeux P R | 2000 | Biochemical Pharmacology2000，59，2： | 1 |
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