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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 | Nitrate accumlation by wheat(Triticum aestivum)in relation to growth and tissue nitrogen concentration显示文摘 | Zhen R G Leigh R A | 1990 | Plant and Soil1990，124，： | 2 |
| 3 | A systematic review and meta-analysis of lower limb neuromuscular alterations associated with knee osteoarthritis during level walking显示文摘 | Mills K Hunt MA Leigh R | 2013 | Clin Biomech (Bristol Avon)2013，28，7： | 1 |
| 4 | 显示文摘 | Leigh R Parameswaran K | 2000 | Am J Respir Crit Care Med2000，161，21： | 1 |
| 5 | Induced spu- tum cell counts in healthy adults显示文摘 | BELDA J LEIGH R PARAMESWARAN K | 2000 | Am J Respir Crit Care Med2000，161，21： | 1 |
| 6 | A Holy Grail of asthma management:toward understanding how long-acting beta(2)-adrenoceptor agonists enhance the clinical efficacy of inhaled corticosteroids显示文摘 | Giembycz MA Kaur M Leigh R | | 0，，： | 1 |
| 7 | Sputum eosinophil count to assess compliance with corticosteroid therapy in asthma 显示文摘 | Parameswaran K Leigh R Hargreave FE | 1999 | J Allergy] Clin Immunol1999，104，： | 1 |
| 8 | 显示文摘 | Leigh R Horsewood P | 2000 | J Allergy Clin Immunol2000，105，61： | 1 |
| 9 | The exploitation of the genome in the search for determinants of virulence in Streptococcus uberis 显示文摘 | LEIGH J A WARD P N FIELD T R | 2004 | Veterinary Immunology and Immunopathology2004，100，： | 1 |
| 10 | Safety of sputum induction in moderate-to-severe smoking-related chronic obstructive pulmonary disease显示文摘 | Wilson AM Leigh R Hargreave FE | 2006 | COPD2006，3，2： | 1 |
| 11 | Potential role for a Carbohydrate moiety in anti-candida activity of human oral epithelial cells 显示文摘 | Steele CH Leigh J Swoboda R | 2001 | Infect And Immun2001，69，11： | 1 |
| 12 | Induced sputum cell counts in healthy adults显示文摘 | Belda J Leigh R Parameswaran K | 2000 | Am J Respir Crit Care Med2000，161，2： | 1 |
| 13 | What is clinical pathway development of a definition to inform the debate显示文摘 | Leigh K Thomas R Erica J | 2010 | BMC Medicine2010，，8： | 1 |
| 14 | Induced sputum cell counts in healthy adults显示文摘 | BELDA J LEIGH R PARAMESWARAN K | 2000 | Am J Respir Crit Care Med2000，161，21： | 1 |
| 15 | Costs differences across demographic groups and types of occupational injuries and illnesses显示文摘 | LEIGH J P WAEHRER C MILLER T R | 2006 | American Journal of Industrial Medicine2006，49，10： | 1 |
| 16 | Augmented reality applications in re-habilitation to improve physical outcomes 显示文摘 | Hussain Al Holger R Leigh H | 2012 | Phys Ther Rev2012，17，1： | 1 |
| 17 | Effects of budesonide and formoterol on allergeninduced airway responses inflammation and airway remodeling in asthma显示文摘 | Leigh R Kelly M | 2010 | J Allergy Clin Immunol2010，125，2： | 1 |
| 18 | Effects of budesonide and formoterol on allergen-induced airway responses, inflammation, and airway remodeling in asthma显示文摘 | Kelly MM O'Connor TM Leigh R | 2010 | J Allergy Clin Immunol2010，125，2： | 1 |
| 19 | Comparison of the utility of barley retrotransposon families for genetic analysis by molecular marker techniques 显示文摘 | Leigh F Kalendar R Lea V | 2003 | Mol Gen Genomincs2003，269，： | 1 |
| 20 | Effects of formoterol-budesonide on airway remodeling in patients with moderate asthma显示文摘 | Pizzichini MM Leigh R | 2006 | Eur Respir J2006，27，5： | 1 |
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