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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 | Retinal damage by light in rats显示文摘 | NOELL W K WALKER V S KANG B S | 1966 | Invest Ophthalmol Vis Sci1966，5，5： | 1 |
| 3 | High speed continuous casting of steel billets Part 2: Mould heat transfer and mould design 显示文摘 | Chow C Samarasekera I V Walker BN etal | 2002 | Ironmaking and Steelmaking2002，29，1： | 1 |
| 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 | Treatment of uterine fibroid tumoar in a nudemonse model using high-intensity focused ultrasound显示文摘 | Vaezy S Fujimoto V Y Walker C | 2000 | American Journal of Obstetrics and Gynecologyl2000，183，1： | 1 |
| 6 | Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals显示文摘 | Scheid J F Mouquet H Feldhahn N Seaman M S Velinzon K Pietzsch J Ott R G Anthony R M Zebroski H Hurley A Phogat A Chakrabarti B Li Y Connors M Pereyra F Walker B D Wardemann H Ho D Wyatt R T Mascola J R Ravetch J V Nussenzweig M C | 2009 | Nature2009，458，7238： | 1 |
| 7 | Epicuticular waxes of two arctic species : compositional differences in relation to winter snow cover显示文摘 | Rieley G Walker J M Callaghan T V | 1995 | Phytochemistry1995，38，： | 1 |
| 8 | Health-related quality of life in patients with major depression who are treated with moclobemide显示文摘 | Walker V Streiner D L Novosel S | 1995 | J Clin Psychopharmacol1995，15，42： | 1 |
| 9 | 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 |
| 10 | Induction of Foxp3 and acquisition of T regulatory activity by stimulated human CD4^+CD25^+ T cells 显示文摘 | WALKER M R KASPROWICZ D J GERSUK V H | 2003 | J Clin Invest2003，112，9： | 1 |
| 11 | Theory and Individual Behavior of First-price Auctions 显示文摘 | Cox J C Smith V L Walker J M | 1988 | Joumal of Risk and Uncertainty1988，1，1： | 1 |
| 12 | The epide- miology and chrono-biology of epistaxis : An investigation of Scottish hospital admissions 1995-2004 显示文摘 | Walker T W Mccfarlane T V Mcgarry G W | 2007 | Clin Oto- laryngol2007，32，5： | 1 |
| 13 | Ammonia toxicity and its prevention in inheriteddefects of the urea cycle 显示文摘 | Walker V | 2009 | Diabetes Obes and Metab2009，11，9： | 1 |
| 14 | Changes in the ultra-low frequency wave field during the precursor phase to the Sichuan earthquake: DEMETER observations显示文摘 | Walker S N Kadirkamanathan V and Pokhotelov O A | 2013 | Ann Geophys2013，31，9： | 1 |
| 15 | An acetal- based PEGylation reagent for pH-sensitive shielding of DNA poly- plexes 显示文摘 | KNORR V ALLMENDINGER L WALKER GF | 2007 | Bioconjugate Chem2007，18，4： | 1 |
| 16 | Synthesis and size control of gold nanoparticles stabilized by poly(methyl- phenylphosphazene)显示文摘 | Walker C H John J V S Wisian Neilson P | 2001 | J Am Chem Soc2001，123，16： | 1 |
| 17 | Recovery of some surface soil properties of ecological interest after sheep grazing in a semi-arid woodland显示文摘 | Braunack M V Walker J | 1985 | Australian Journal of Ecology1985，10，4： | 1 |
| 18 | Effects of hypoxia on urinary organic acid and hypoxanthine excretion in fetal sheep显示文摘 | Walker V Bennet L Mills GA | 1996 | Pediatr Res1996，40，： | 1 |
| 19 | Pretransplantation seronegative Epstein-Barr virus status is the primary risk factor for posttransplantation lymphoproliferative disorder in adult heart,lung, and other solid organ transplantations 显示文摘 | Walker R C Paya C V Marshall W F | 1995 | J Heart Lung Transplant1995，14，： | 1 |
| 20 | miR-19 is a key oncogenic component of mir-17-92 显示文摘 | Olive V Bennett M J Walker J C | 2009 | Genes Dev2009，23，24： | 1 |
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