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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 | 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 |
| 3 | The natural history of nonalco2holic,steatohepatitis:a follow-up study of forty-two patients for up to 21 years显示文摘 | Elizabeth E Powell W Graham E | 1990 | Hepatology1990，11，1： | 1 |
| 4 | Medication beliefs predict medication adherence in ambulatory patients with decompensated cirrhosis显示文摘AIM To investigate the impact of medication beliefs, illness perceptions and quality of life on medication adherence in people with decompensated cirrhosis.METHODS One hundred adults with decompensated cirrhosis completed a structured questionnaire when they attended for routine outpatient hepatology review. Measures of self-reported medication adherence(Morisky Medication Adherence Scale), beliefs surrounding medications(Beliefs about Medicines Questionnaire), perceptions of illness and medicines(Brief Illness Perception Questionnaire), and quality of life(Chronic Liver Disease Questionnaire) were examined. Clinical data were obtained via patient history and review of medical records. Least absolute shrinkage and selection operator and stepwise backwards regression techniques were used to construct the multivariable logistic regression model. Statistical significance was set at alpha = 0.05.RESULTS Medication adherence was ' High ' in 42 % o f participants, 'Medium' in 37%, and 'Low' in 21%. Compared to patients with 'High' adherence, those with 'Medium' or 'Low' adherence were more likely to report difficulty affording their medications(P < 0.001), lower perception of treatment helpfulness(P = 0.003) and stronger medication concerns relative to medication necessity beliefs(P = 0.003). People with 'Low' adherence also experienced greater symptom burden and poorer quality of life, including more frequent abdominal pain(P = 0.023), shortness of breath(P = 0.030), and emotional disturbances(P = 0.050). Multivariable analysis identified having stronger medication concerns relative to necessity beliefs(Necessity-Concerns Differential ≤ 5, OR = 3.66, 95%CI: 1.18-11.40) and more frequent shortness of breath(shortness of breath score ≤ 3, OR = 3.87,95%CI: 1.22-12.25) as independent predictors of 'Low'adherence.CONCLUSION The association between 'Low' adherence and patients having strong concerns or doubting the necessity or helpfulness of their medications should be explored further given the clinical relevance. | Kelly L Hayward Patricia C Valery Jennifer H Martin Antara Karmakar Preya J Patel Leigh U Horsfall Caroline J Tallis Katherine A Stuart Penny L Wright David D Smith Katharine M Irvine Elizabeth E Powell W Neil Cottrell | 2017 | World Journal of Gastroenterology2017，23，40： | 1 |
| 5 | 肝移植受者IL-10基因启动子多态性与急性排斥反应的关系显示文摘目的 探讨肝移植受者白细胞介素 10 (IL 10 )基因多态性与急性排斥反应的关系。方法 应用PCR限制性片段长度多态性分析法 ,检测 12 2例肝移植受者IL 10基因启动子的 2个多态位点 - 10 82和 - 5 92的各种基因型的分布 ,并分析它们与急性排斥反应的关系。结果 IL 10 - 5 92位点 ,A/A ,C/A ,C/C等基因型间的急性排斥反应发生率分别为 16.7%,19%,2 9%,相互比较 ,差异不显著 (P >0 .0 5 ) ;IL 10 - 10 82位点 ,尽管G/G基因型的急性排斥反应发生率 ( 3 3 %)高于A/A型( 18%) ,但差异仍不显著 (P >0 .0 5 )。结论 IL 10基因多态性与肝移植受者术后急性排斥反应无确切关系。 | 崔宏 Julie R Jonsson Cathy Edwards Smith Elizabeth E Powell | 2001 | 中华器官移植杂志2001，22，4： | 0 |
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