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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 | Biology of Trichogramma ostriniae (Hymenoptera: Trichogrammatidae) reared on Ostriniae nubilalis (Lepidoptera: Pyralidae) and survey for additional hosts显示文摘 | HOFFMANN M P WALKER D L SHELTON A M | 1998 | Entomophaga1998，40，： | 2 |
| 3 | The role of periodic agitation and water addition in managing moisture limitations during high-solids aerobic decomposition显示文摘 | Walker L P Nock T D Gossett J M VanderGheynst J S | 1999 | Process Biochemistry1999，34，： | 2 |
| 4 | Atmospheric transport and wet deposition of ammonium in North Carolina 显示文摘 | Walker J T Aneja V P Dickey D A | 2000 | Atmospheric Environment2000，34，20： | 1 |
| 5 | The effect of temperature and relative humidity on population growth of three Liposcelis infesting stored products in tropical countries 显示文摘 | Ree D P Walker A G | 1990 | Bolletin of Entom Res1990，80，： | 1 |
| 6 | SGrid: A Service- Oriented Model for the Semantic Grid显示文摘 | Li M van Santen P Walker D W | 2004 | Future Generation Computer Systems2004，20，1： | 1 |
| 7 | 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 |
| 8 | Grid: a service-oriented model for the Semantic Grid显示文摘 | Li M A Santen P V Walker D W | 2004 | Future Generation Computer Systems2004，20，： | 1 |
| 9 | 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 |
| 10 | Activity studies of eight purified cellulases:specificity,synergism and binding domain effects显示文摘 | IRWIN D SPEZIO M WALKER L P | 1993 | Biotechnol Bioeng1993，42，： | 1 |
| 11 | The effect of temperature and relative humidity on population growth of three Liposcelis species (Psocoptera:Liposcelidae) infesting stored products in tropical countries显示文摘 | Rees D P and Walker A J | 1990 | Bulletin of Entomological esearch1990，，80： | 1 |
| 12 | Cardiac T2* Magnetic Resonance for Prediction of Cardiac Complications in Thalassemia Major显示文摘 | P Kirk M Roughton J B. Porter J M. Walker M A. Tanner J Patel D Wu J Taylor M A. Westwood L J. Anderson D J. Pennell | 2009 | Circulation2009，，20： | 1 |
| 13 | 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 |
| 14 | 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 |
| 15 | Cesium removel from high-pH,high-salt wastewater using crystalline silicotitanate sorbent显示文摘 | Jr WALKER J F TAYLOR P A LEE D D | 1999 | Separation Science and Technology1999，34，67： | 1 |
| 16 | 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 |
| 17 | Contamination-free sounding rocket Langmuir probe显示文摘 | AMATUCCI W E SCHUCK P W WALKER D N etal | 2001 | Review of Scientific Instrumnets2001，72，4： | 1 |
| 18 | The efficiency and mechanism of densification of 2-D C/C composites by coaltar pitch impregnation显示文摘 | Matzinos P D Patrick J W Walker A | 2000 | Carbon2000，38，： | 1 |
| 19 | 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 |
| 20 | A case of isolated primary chylopericardium显示文摘 | Ross P Joseph S Walker D | 1979 | Br Heart J1979，41，： | 1 |
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