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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 | Calcium-stimulated autophosphorylation site of plant chimeric calcium/calmodulin dependent protein kinase显示文摘 | SATHYANARAYANAN P V SIEMS W F JONES J P POOVAISH B W | 2001 | Journal of Biological Chemistry2001，276，32： | 1 |
| 3 | DNA methylation decreases in aging but not in immortal cells显示文摘 | Wilson V L Jones P A | 1988 | Science1988，220，： | 1 |
| 4 | Venous thromboem- bolism after spinal cord injury: incidence, time course, and associated risk factors in 16, 240 adults and children 显示文摘 | Jones T Ugalde V Franks P | 2005 | Arch Phys Med Rehabil2005，86，12： | 1 |
| 5 | Nucleotide sequence and genome organization of canine parvovirus 显示文摘 | Reed A P Jones E V Miller T J | 1988 | J Virol1988，62，： | 1 |
| 6 | Effects of estrogen ex- posure and reproductive factors on bone mineral density and osteopo- rotic fractures 显示文摘 | Nguyen T V Jones G Sambrook P N | 1995 | Clin Endocrinol Metab1995，80，9： | 1 |
| 7 | Two monoclonal an tibodies(cc17,cc29)recognizing an antigen(Bo5)on bovine T lymphocytes,analogous to human CD5显示文摘 | Howard C J,Parsons K P,Jones B V | 1988 | Vet Immunol1988，13，： | 1 |
| 8 | Critical evaluation of organic acid mediated iron dissolution in the rhizosphere and its potential role in root iron uptake显示文摘 | Jones D L Darrab P R Kochian L V | 1996 | Plant Soil1996，180，： | 1 |
| 9 | Critical-evaluation of organic-acid mediated iron dissolution in the rhizosphere and its potential role in root iron uptake显示文摘 | JONES D L DARRAH P R KOCHIAN L V | 1996 | Plant and soil1996，180，： | 1 |
| 10 | Elimination of endocrine disrupting chemicals nonylphenol and bisphenol A and personal care product ingredient triclosan using enzyme preparation from the white rot fungus Coriolopsis polyzona显示文摘 | Cabana H Jiwan J L H Rozenberg R Elisashvili V Penninckx M Agathos S N Jones J P | 2007 | Chemosphere2007，67，4： | 1 |
| 11 | DNA methylation decreases in aging but not in immortal cells显示文摘 | Wilson V L Jones P A | 1983 | Science1983，220，4601： | 1 |
| 12 | Activity of the plasma membrane H+ -ATPase is a key physiologi- cal determinant of thermotolerance in Saccharomyces cerevisiae 显示文摘 | Coote P J Jones M V Seymour I J | 1994 | Microbiology1994，140，8： | 1 |
| 13 | A new perspective on recent global warming:asymmetric trends of daily maximum and minimum temperature显示文摘 | Karl T R Jones P D Knight R W Kukla G Plumm-er N Razuvayev V Gallo K P Lindseay J Charison R J Peterson T C | 1993 | Bull Amer Meteor Soc1993，74，6： | 1 |
| 14 | Habitat biodiversity as a determinant of fish community structure on coral reefs显示文摘 | Messmer V Jones G P Munday P L | 2011 | Ecology2011，92，12： | 1 |
| 15 | Decision Making in a Sequential Search Task 显示文摘 | Kahan J P Rapoport A Jones L V | 1967 | Perception and Psychophysics1967，2，8： | 1 |
| 16 | Critical evaluation of organic acid mediated iron dissolution in the rhizosphere and its potential role in root iron uptake显示文摘 | Jones D L Darrah P R Dochian L V | 1996 | Plant and Soil1996，180，： | 1 |
| 17 | Extracting and improving microarchitecture performance on reconfigurable architectures显示文摘 | Padmanabhan S Jones P Schuehler D V | 2005 | International Journal of Parallel Programming2005，33，23： | 1 |
| 18 | Nucleotide Sequence and Genome Organization of Canine Parvovirus 显示文摘 | Reed A P Jones E V Miller T J | 1988 | Journal of Virology1988，1，： | 1 |
| 19 | Radiometric dating of lake sediments from Signy Island(maritime Antarctic):evidence of recent climatic change显示文摘 | APPLEBY P G JONES V J ELLIS-EVANS J C | 1995 | Paleolimnology1995，13，： | 1 |
| 20 | Liquid crystal measure ments of heat transfer and surface shear stress 显示文摘 | IRELAND P T JONES T V | 2000 | Measurement Science and Technology2000，11，7： | 1 |
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