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Macrophage secretory products induce an inflammatory phenotype in hepatocytes

World Journal of Gastroenterology 2012年第15期18卷 1732-1744页

作者： 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 Centre for Liver Disease Research School of MedicineThe University of QueenslandPrincess Alexandra HospitalBrisbane 4102QueenslandAustralia Department of Gastroenterology and Hepatology Princess Alexandra HospitalBrisbane 4102QueenslandAustralia Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre The University of QueenslandBrisbane 4072QueenslandAustralia Diamantina Institute The University of QueenslandBrisbane 4102QueenslandAustralia

AIM:To investigate the influence of macrophages on hepatocyte phenotype and ***: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 *** in vivo relevance of these findings was confirmed using liver biopsies from 147 patients with hepatitis C virus(HCV)***: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 *** 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 *** 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 *** 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 *** 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 ***:Secreted macrophage products alter the phenotype and function of hepatocytes,with increased expression of inflammatory mediators,suggesting that hepatocytes actively participat

关键词：细胞分泌肝细胞诱导 mRNA表达 HepG2细胞丙型肝炎病毒转化生长因子 MMP-9

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Senescent human hepatocytes express a unique secretory phenotype and promote macrophage migration

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World Journal of Gastroenterology 2014年第47期20卷 17851-17862页

作者： 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 Centre for Liver Disease Research School of MedicineThe University of QueenslandTranslational Research InstituteBrisbane 4102Australia Institute for Molecular Bio-science The University of QueenslandBrisbane 4067Australia The University of Queensland Diamantina Institute The University of Queensland Translational Research InstituteBrisbane 4102Australia Department of Gastroenterology and Hepatology Princess Alexandra HospitalBrisbane 4102Australia

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 *** was confirmed by cytochemical staining for a panel of markers including Ki67,p21,heterochromatin protein 1β,and senescence-associated-β-galactosidase *** 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 ***:Senescent hepatocytes induced classical markers of senescence(p21,heterochromatin protein1β,and senescence-associated-β-galactosidase activity);and downregulated the proliferation marker,*** senescence induced a 4.6-fold increase in total secreted protein(P=0.06)without major alterations in the protein ***-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 *** 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 *** 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 ***:Our novel model of hepatocyte senescence provides insights into mechanisms by which senescent hepatocytes may promote chronic liver disease pathogenesis.

关键词： Cell aging Chemokines Hepatocytes Inflammation Liv

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Comparison of the Refraction Precision Results between Pentacam AXL and IOL Master 700 Using Universal II Barrett Formula after Cataract Surgery

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Open Journal of Ophthalmology 2023年第1期13卷 1-12页

作者： Budiman Tjokrovonco Ludwig melino Sugiarti Emmy Dwi Knoch Andrew Maximilian Cataract and Refractive Surgery Unit Cicendo National Eye Center Bandung Bandung Indonesia Department of Ophthalmology Faculty of Medicine Universitas Padjajaran/National Eye Center - Cicendo Eye Hospital Bandung Indonesia

Background: The availability of premium intraocular lenses (IOL), including toric, multifocal, and EDOF, has become very sophisticated and now demands accurate biometric measurement accuracy. The Pentacam AXL and IOL Master 700 are often used for optical biometry and they are available in the market today. They can also be used to measure the parameters needed in the IOL calculation using the latest generation formulas, such as the Barett Universal II. Therefore, this study aims to compare the accuracy of refraction results between Pentacam AXL compared to IOL Master 700 after cataract surgery with the Barett Universal-II formula. Method: A total of 64 eyes from 64 patients who had a preoperative examination with IOL Master 700 and Pentacam AXL were included in this study. Parameters such as K, ACD, LT, WTW, and AL were then compared between the two tools. Prediction error values were also calculated and compared based on the difference between the Spherical equivalent (SE) of subjective refraction results after 4 weeks of surgery with their refractive prediction targets. Results: There was no statistically significant difference in the parameters measured from the two tools except ACD and WTW. Furthermore, LT was difficult to obtain on the Pentacam AXL due to penetration problems, as well as in patients with significant lens opacities. The percentage of error prediction values that reach ± 0.50 D on Pentacam AXL and IOL Master 700 was 70.3% and 73.5%, respectively. However, the average prediction error that was close to emmetropia with IOL Master 700 was greater compared to the other tool. Conclusion: Pentacam AXL has a fairly good accuracy for refraction prediction compared to IOL Master 700. However, it is still necessary to optimize its constants to obtain optimal results.

关键词： Error Prediction Biometry IOL Master 700 Pentacam AXL

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Cell death, the p53 family, and cancer

Cell death, the p53 family, and cancer

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中国生物化学与分子生物学会第十一次会员代表大会暨201...

作者： melino G MRC Toxicology Unit Leicester LE1 9HN UK University of Rome Tor Vergata 00133 Rome Italy

In the last ten years,p63 and p73 have been identified as the ancestral members of the p53 *** the high sequence and structural similarity,the mouse knockouts revealed a crucial role in neural development for p73 and in epidermal formation for *** identified several transcriptional targets,the mechanisms of regulation of cell death,and the p63 isoform involved in epithelial *** genes are involved in female infertility and maternal reproduction(AJ Levine,Nature Rev MCB 2011)as well as in cancer formation(G melino,CDD 2011;P Tucci PNAS-USA 2012),although with distinct ***73 knockout mice(TW Mak,G&D 2008)show high tumor incidence with hippocampal dysegensis(M Agostini,PNAS-USA 2012).Conversely,ΔNp73 knockout mice(TW Mak,G&D 2010)

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CSF-1-dependant Bone Marrow Derived Macrophages Mediate Chronic Graft-Versus-Host Disease

CSF-1-dependant Bone Marrow Derived Macrophages Mediate Chro...

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第九届全国免疫学学术大会

作者： Alexander KA Flynn R Lineburg KE Kuns RD Teal BE Olver SD Lor M Raffelt NC Koyama M Leveque L Le Texier L melino M Markey KA Varelias A Engwerda CR Serody J Janela B Ginhoux F Clouston AD Blazar BR Hill GR MacDonald KPA QIMR Berghofer Medical Research Institute Brisbane4006Australia Pediatric Blood and Marrow Transplantation Program University of MinnesotaMinneapolisMN 55454USA Lineberger Comprehensive Cancer Center University of North Carolina School of MedicineChapel HillNCUSA Singapore Immunology Network(SIgN) A*STAR(Agency for ScienceTechnology and Research)Biopolis138648 Singapore Department of Bone Marrow Transplantation Royal Brisbane HospitalBrisbane4006Australia

Chronic GVHD(cGVHD)is the major cause of late non-relapse death following stem cell transplantation which targets organs such as skin and *** multiple models of cGVHD we investigated the role of macrophages in the development of *** an established IL-17 dependent sclerodermatous cGVHD model,we confirmed that macrophages

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