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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 | Black Cohosh and other Jherbal remedies associated with acute hepatitis 显示文摘 | Whiting PW Clouston A Kerlin P | 2002 | Med Aust2002，177，8： | 1 |
| 4 | Independent effects of diet and exercise training on fat oxidation in non-alcoholic fatty liver disease显示文摘AIM To investigate the independent effects of 6-mo of dietary energy restriction or exercise training on wholebody and hepatic fat oxidation of patients with nonalcoholic fatty liver disease(NAFLD).METHODS Participants were randomised into either circuit exercise training(EX;n = 13;3 h/wk without changes in dietary habits),or dietary energy restriction(ER) without changes in structured physical activity(ER;n = 8).Respiratory quotient(RQ) and whole-body fat oxidation rates(Fatox) were determined by indirect calorimetry under basal,insulin-stimulated and exercise conditions.Severity of disease and steatosis was determined by liver histology;hepatic Fatox was estimated from plasma β-hydroxybutyrate co.ncentrations;cardiorespiratory fitness was expressed as VO2 peak.Complete-case analysis was performed(EX:n = 10;ER:n = 6).RESULTS Hepatic steatosis and NAFLD activity score decreased with ER but not with EX.β-hydroxybutyrate concentrations increased significantly in response to ER(0.08 ± 0.02 mmol/L vs 0.12 ± 0.04 mmol/L,P = 0.03) but remained unchanged in response to EX(0.10 ± 0.03 mmol/L vs 0.11 ± 0.07 mmol/L,P = 0.39).Basal RQ decreased(P = 0.05) in response.to EX,while this change was not significant after ER(P = 0.38).VO_(2peak)(P < 0.001) and maximal Fa_(tox) during aerobic exercise(P = 0.03) improved with EX but not with ER(P > 0.05).The increase in β-hydroxybutyrate concentrations was correlated with the reduction in hepatic steatosis(r =-0.56,P = 0.04).CONCLUSION ER and EX lead to specific benefits on fat metabolism of patients with NAFLD.Increased hepatic Fat_(ox) in response to ER could be one mechanism through which the ER group achieved reduction in steatosis. | Ilaria Croci Nuala M Byrne Veronique S Chachay Andrew P Hills Andrew D Clouston Trisha M O'Moore-Sullivan Johannes B Prins Graeme A Macdonald Ingrid J Hickman | 2016 | World Journal of Hepatology2016，8，27： | 1 |
| 5 | The influence of voluntary EMG activity and click intensity on the vestibular click evoked myogenic potential显示文摘 | Lim CL Clouston P Sheean G | 1995 | Muscle Nerve1995，18，： | 1 |
| 6 | A low- technology approach toward fabrication of laminated bamboo lumber显示文摘 | MAHDAVI M CLOUSTON P L ARWADE S R | 2012 | Construction and Building Materials2012，43，29： | 1 |
| 7 | Shear and Ben- ding Performance of a Novel Wood-Concrete Composite System显示文摘 | Clouston P Bathon L A Schreyer A | 2005 | Journal of Structural Engineering2005，131，9： | 1 |
| 8 | Steatosis inehronic hep- atitis C:association withinereased messengerRNA expression of collagen I, tumor necrosis factor - alphaand cytoc hrome P4502E1 显示文摘 | Gochee P A Jonsson J R Clouston N D | 2003 | J GastroenteroI Hepatol2003，18，4： | 1 |
| 9 | Measurement of ane- choic chanber reflections by time-domain techniques 显示文摘 | Clouston E N Langsford P A Evans S | 1988 | IEEE PROCEEDINGS1988，135，2： | 1 |
| 10 | Development of laminat- ed bamboo lumber: review of processing, performance, and eco- nomical consideration显示文摘 | Mahdavi M Clouston P L Arwade S R | 2011 | Journal of Materials in Civil Engineer- ing2011，23，7： | 1 |
| 11 | Steatosis in chronic hepatitis C: association with increased messenger RNA expression of collagen I,tumor necrosis factor-alpha and cytochrome P450 2El显示文摘 | GOCHEE P A JONSSON J R CLOUSTON A D | 2003 | J Gastroenterol Hepatol2003，18，4： | 1 |
| 12 | Quantitative studies of F responses in Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy显示文摘 | Kiers L Clouston P Zuniga G | 1994 | Electroencephalogr Clin Neurophysiol1994，93，： | 1 |
| 13 | The current use of botulinum toxin 显示文摘 | MAHANT N CLOUSTON P D LORENTZ I T | 2000 | Janrnal of Clinical Neuroscience2000，7，5： | 1 |
| 14 | Parasitic origin of a solitary necrotic nodule of the liver显示文摘 | Clouston A D Walker N I Prociv P | 1993 | J Clin Pathol1993，46，： | 1 |
| 15 | Experimental behavior of a continuous metal connector for a wood- concrete composite system 显示文摘 | CLOUSTON P CIVJAN S BATHON L | 2004 | Forest Products Journal2004，54，6： | 1 |
| 16 | Parastitic origin of a solitary necrotic nodule of the liver显示文摘 | Clouston AD Walker NI Prociv P | 1993 | J Clin Pathol1993，46，6： | 1 |
| 17 | The influence of voluntary EMG activity and click intensity on the vestibular click evoked myogenic potential显示文摘 | Lim CL Clouston P Sheean G | | 0，，10： | 1 |
| 18 | The influence of voluntary EMG activity and click intensi- ty on the vestibular click evoked myogenic potential 显示文摘 | LIM C L CLOUSTON P SHEEAN G | 1995 | Muscle Nerve1995，18，： | 1 |
| 19 | Initiation of germination and inactivation of Bacillus pumilus spores by hydrostatic pressure显示文摘 | Clouston J G Wills P A | 1969 | J Bacteriol1969，97，： | 1 |
| 20 | Gamma radiation - initiated polymerization of styrene at high pressure 显示文摘 | Moore P W Clouston J G | 1983 | Polym Sci : Polym Chem Ed1983，21，： | 1 |
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