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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 | Performance limiting micropipe defects in silicon carbide wafers 显示文摘 | NEUDECK P G POWELL J A | 1994 | IEEE Electron Device Lett1994，15，： | 2 |
| 3 | Senescent human hepatocytes express a unique secretory phenotype and promote macrophage migration显示文摘AIM:To develop a model of stress-induced senescence to study the hepatocyte senescence associated secretory phenotype(SASP).METHODS:Hydrogen peroxide treatment was used to induce senescence in the human Hep G2 hepatocyte cell line.Senescence was confirmed by cytochemical staining for a panel of markers including Ki67,p21,heterochromatin protein 1β,and senescence-associated-β-galactosidase activity.Senescent hepatocytes were characterised by gene expression arrays and quantitative polymerase chain reaction(q PCR),and conditioned media was used in proteomic analyses,a human chemokine protein array,and cell migration assays to characterise the composition and function of the hepatocyte SASP.RESULTS:Senescent hepatocytes induced classical markers of senescence(p21,heterochromatin protein1β,and senescence-associated-β-galactosidase activity);and downregulated the proliferation marker,Ki67.Hepatocyte senescence induced a 4.6-fold increase in total secreted protein(P=0.06)without major alterations in the protein profile.Senescence-induced genes were identified by microarray(Benjamini Hochbergcorrected P<0.05);and,consistent with the increase in secreted protein,gene ontology analysis revealed a significant enrichment of secreted proteins among inducible genes.The hepatocyte SASP included characteristic factors such as interleukin(IL)-8 and IL-6,as well as novel components such as SAA4,IL-32and Fibrinogen,which were validated by q PCR and/or chemokine protein array.Senescent hepatocyteconditioned medium elicited migration of inflammatory(granulocyte-macrophage colony stimulating factor,GM-CSF-derived),but not non-inflammatory(CSF-1-derived)human macrophages(P=0.022),which could contribute to a pro-inflammatory microenvironment in vivo,or facilitate the clearance of senescent cells.CONCLUSION:Our novel model of hepatocyte senescence provides insights into mechanisms by which senescent hepatocytes may promote chronic liver disease pathogenesis. | Katharine M Irvine Richard Skoien Nilesh J Bokil Michelle Melino Gethin P Thomas Dorothy Loo Brian Gabrielli Michelle M Hill Matthew J Sweet Andrew D Clouston Elizabeth E Powell | 2014 | World Journal of Gastroenterology2014，20，47： | 2 |
| 4 | Delay of disease development in transgenic plant that express the tobacco mosaic virus coat protein gene显示文摘 | Powell A P Nelson R S De B | 1986 | Science1986，232，： | 2 |
| 5 | Situ immunoassay (ISIA)of field grapefruit trees inoculated with mild isolates of citrus tristeza virus indicates mixed infections with severe isolates显示文摘 | Youjian L Rundell P A Powell C A | 2002 | Plant Disease2002，，86： | 2 |
| 6 | Bit-wise paral lel algorithms for efficient software correlation applied to a GPS soft ware receiver显示文摘 | LEDVINA B M PSIAKI M L POWELL S P | 2004 | IEEE Transactions on Wireless Communications2004，3，5： | 1 |
| 7 | Growth and sexual size dimorphism in Alberta populations of the eastern short-homed lizard,Phrynosoma douglassi brevirostre 显示文摘 | POWELL G L RUSSELL A P | 1985 | Can J Zool1985，63，： | 1 |
| 8 | The iron cage revisited:Institu-tional isomorphism and collective rationality in organizational fields显示文摘 | DiMaggio P J and Powell W | 1983 | American Sociological Review1983，48，2： | 1 |
| 9 | Construc- tion of Rhodococcus random mutagenesis libraries u- sing Tn5 transposition complexes 显示文摘 | Fernandes P J Powell J A C Archer J A (2 | 2001 | Mierobiology- Sgm2001，147，： | 1 |
| 10 | Supporting cancer patients' unanchored health information management with mobile technology显示文摘 | Klasnja P Hartzler A Powell C | 2011 | AMIA Annu Symp Proc2011，2011，： | 1 |
| 11 | A double blind, randomized, controlled trial of glutamine supplementation in parenteral nutrition显示文摘 | Powell T J Jamieson C P Bettany G E | 1999 | Gut1999，45，1： | 1 |
| 12 | Delay of disease development in transgenic plants that express the tobacco mosaic virus coat protein gene显示文摘 | Powell Abel P Nelson R S De B | 1986 | Science1986，232，： | 1 |
| 13 | Reduced drag coefficient for high wind speeds in tropical cyclones显示文摘 | POWELL M D VICKERY P J REINHOLD T A | 2003 | Nature2003，422，： | 1 |
| 14 | Wind-driven surface transport in stratified closed basins: Direct versus residual circulations显示文摘 | Strub P T Powell T M | 1986 | Journal of Geophysical Research1986，91，7： | 1 |
| 15 | Hydraulic conductivity of a recent estuarine silty clay at Bothkennar显示文摘 | LEROUEIL S LERAT P HIGHT D W POWELL J J M | 1992 | Geotechnique1992，42，2： | 1 |
| 16 | Reduced drag coefficient for high wind speeds in tropical cyclones 显示文摘 | POWELL M D VICKERY P J REINHOLD T A | 2005 | Nature2005，422，6929： | 1 |
| 17 | Brain metastases from papillary thyroid carcinomas 显示文摘 | Tahmasebi EC Farmer P Powell SZ | 2013 | Virchows Arch2013，462，4： | 1 |
| 18 | Evaluation of CHROMagar Candida for Presumptive Identification of Clinically Important Candida Species显示文摘 | Heather L Powell Crystal A Sand Robert P Rennie | 1998 | Diagn Microbiol Infect Dis1998，32，4： | 1 |
| 19 | Information systems strategy for small and medium sized enterprises:An organization perspective显示文摘 | LEVY M POWELL P | 2000 | Strategic Information systems2000，，9： | 1 |
| 20 | Model-based air-fuel ratio control in SI engines with a switch-type EGO sensor 显示文摘 | Amstutz A Fekete N P Powell J D | 1994 | SAE Transactions Section 3 Journal of Engines1994，1994，103： | 1 |
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