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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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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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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 Pment 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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