Intrasplenic transplantation of IL-18 gene-modified hepatocytes: an effective approach to reverse hepatic fibrosis in schistosomiasis through induction of dominant Th1 response.

Abstract:

:Hepatic fibrosis is a common outcome of chronic liver diseases. In schistosomiasis, chronic parasite egg-induced granuloma formation can lead to fibrosis, which is immunologically characterized by the dominant Th2 response. Recently, it has been shown that gene therapy is an attractive approach for the treatment of hepatic fibrosis. To investigate the antifibrotic effects of IL-18 gene transfer, a normal murine liver cell line BNL.CL2 was transfected with recombinant adenovirus encoding mouse IL-18, and then intrasplenically transplanted into mice infected with Schistosoma japonicum (S. japonicum). Our data show that IL-18 gene-modified hepatocytes intrasplenically transplanted into mice can effectively express IL-18 in the liver and in peripheral blood. Intrasplenic transplantation of IL-18 gene-modified hepatocytes into S. japonicum-infected mice could result in a significantly increased IFN-gamma and IL-2 but decreased IL-4 and IL-10 concentration both in the liver and in the serum, suggesting that the dominant Th2 response in mice with schistosomiasis could be reversed by this intervention. Consistent with the changes in Th1 and Th2 cytokine production, mice intrasplenically transplanted with IL-18 gene-modified hepatocytes developed much less hepatic fibrosis at 20 weeks after infection, which was evaluated by liver content of hydroxyproline, collagens, and hepatic mRNA expression of procollagens. These data indicate that intrasplenic transplantation of IL-18 gene-modified hepatocytes can be a candidate for therapeutic intervention in hepatic fibrosis through induction of a dominant Th1 response.

journal_name

Gene Ther

journal_title

Gene therapy

authors

Zhang LH,Pan JP,Yao HP,Sun WJ,Xia DJ,Wang QQ,He L,Wang J,Cao X

doi

10.1038/sj.gt.3301524

keywords:

subject

Has Abstract

pub_date

2001-09-01 00:00:00

pages

1333-42

issue

17

eissn

0969-7128

issn

1476-5462

journal_volume

8

pub_type

杂志文章
  • Gene therapy in autoimmune, demyelinating disease of the central nervous system.

    abstract::Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS), where suspected autoimmune attack causes nerve demyelination and progressive neurodegeneration and should benefit from both anti-inflammatory and neuroprotective strategies. Although neuroprotection strategies are relatively une...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/sj.gt.3302025

    authors: Baker D,Hankey DJ

    更新日期:2003-05-01 00:00:00

  • Co-expression of p21(Waf1/Cip1) in adenovirus vectors improves expression of a second transgene.

    abstract::First-generation adenoviral (Ad) vectors are frequently used vectors for experimental and clinical gene transfer. Earlier it has been shown that parallel overexpression of the cell cycle regulator p21(Waf1/Cip1) (p21) or antiapoptotic bcl-2 from a second vector reduces cytotoxicity and improves transgene expression. H...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2009.2

    authors: Schumacher A,Horvat S,Woischwill C,Wolff G,Witt C

    更新日期:2009-04-01 00:00:00

  • Imaging the spatial distribution of transgene expression in the lungs with positron emission tomography.

    abstract::This study was designed to evaluate the utility of positron emission tomography (PET) to quantify the magnitude and spatial distribution of transgene expression after different methods of adenoviral vector delivery (with surfactant- and saline-based vehicles) within rat lungs. In all, 17 animals (eight in the surfacta...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302117

    authors: Richard JC,Factor P,Welch LC,Schuster DP

    更新日期:2003-12-01 00:00:00

  • Effect of tolerance induction to immunodominant T-cell epitopes of Sendai virus on gene expression following repeat administration to lung.

    abstract::Sendai virus (SeV) is able to transfect airway epithelial cells efficiently in vivo. However, as with other viral vectors, repeated administration leads to reduced gene expression. We have investigated the impact of inducing immunological tolerance to immunodominant T-cell epitopes on gene expression following repeate...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302677

    authors: Griesenbach U,Boyton RJ,Somerton L,Garcia SE,Ferrari S,Owaki T,Ya-Fen Z,Geddes DM,Hasegawa M,Altmann DM,Alton EW

    更新日期:2006-03-01 00:00:00

  • Lethal toxicity caused by expression of shRNA in the mouse striatum: implications for therapeutic design.

    abstract::Therapeutic RNA interference (RNAi) has emerged as a promising approach for the treatment of many incurable diseases, including cancer, infectious disease or neurodegenerative disorders. Demonstration of efficacy and safety in animal models is necessary before planning human application. Our group and others have prev...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2011.10

    authors: Martin JN,Wolken N,Brown T,Dauer WT,Ehrlich ME,Gonzalez-Alegre P

    更新日期:2011-07-01 00:00:00

  • Fibroblasts modulate cardiomyocyte excitability: implications for cardiac gene therapy.

    abstract::In an earlier study exploring the potential of gene transfer to repair myocardial conduction defects, we observed that myotubes, generated by forced expression of MyoD, exhibit reduced excitability when also modified to express connexin43 (Cx43). We hypothesized that this effect was caused by gap junction-mediated cou...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302813

    authors: Kizana E,Ginn SL,Smyth CM,Boyd A,Thomas SP,Allen DG,Ross DL,Alexander IE

    更新日期:2006-11-01 00:00:00

  • Development of a nonintegrating Rev-dependent lentiviral vector carrying diphtheria toxin A chain and human TRAF6 to target HIV reservoirs.

    abstract::Persistence of human immunodeficiency virus (HIV) despite highly active antiretroviral therapy (HAART) is a lasting challenge to virus eradication. To develop a strategy complementary to HAART, we constructed a series of Rev-dependent lentiviral vectors carrying diphtheria toxin A chain (DT-A) and its attenuated mutan...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2010.53

    authors: Wang Z,Tang Z,Zheng Y,Yu D,Spear M,Iyer SR,Bishop B,Wu Y

    更新日期:2010-09-01 00:00:00

  • β1-Na(+),K(+)-ATPase gene therapy upregulates tight junctions to rescue lipopolysaccharide-induced acute lung injury.

    abstract::Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with diverse disorders and characterized by disruption of the alveolar-capillary barrier, leakage of edema fluid into the lung, and substantial inflammation leading to acute respiratory failure. Gene therapy is a potentially powerful...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2016.19

    authors: Lin X,Barravecchia M,Kothari P,Young JL,Dean DA

    更新日期:2016-06-01 00:00:00

  • PDGF-B gene therapy accelerates bone engineering and oral implant osseointegration.

    abstract::Platelet-derived growth factor-BB (PDGF-BB) stimulates repair of healing-impaired chronic wounds such as diabetic ulcers and periodontal lesions. However, limitations in predictability of tissue regeneration occur due, in part, to transient growth factor bioavailability in vivo. Here, we report that gene delivery of P...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2009.117

    authors: Chang PC,Seol YJ,Cirelli JA,Pellegrini G,Jin Q,Franco LM,Goldstein SA,Chandler LA,Sosnowski B,Giannobile WV

    更新日期:2010-01-01 00:00:00

  • Formation of LID vector complexes in water alters physicochemical properties and enhances pulmonary gene expression in vivo.

    abstract::There is currently an urgent need to develop efficient gene-delivery systems for the lung that are free of inflammatory effects. The LID vector is a synthetic gene delivery system, comprised of lipofectin (L), an integrin-targeting peptide (I) and DNA (D) that has previously been shown to have high transfection effici...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301963

    authors: Jenkins RG,Meng QH,Hodges RJ,Lee LK,Bottoms SE,Laurent GJ,Willis D,Ayazi Shamlou P,McAnulty RJ,Hart SL

    更新日期:2003-06-01 00:00:00

  • Overexpression of PAI-1 prevents the development of abdominal aortic aneurysm in mice.

    abstract::Vessel wall inflammation and matrix destruction are critical to abdominal aortic aneurysm (AAA) formation and rupture. We have previously shown that urokinase plasminogen activator (uPA) is highly expressed in experimental AAA and is essential for AAA formation and expansion. In this study, we examined the effects of ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3303069

    authors: Qian HS,Gu JM,Liu P,Kauser K,Halks-Miller M,Vergona R,Sullivan ME,Dole WP,Deng GG

    更新日期:2008-02-01 00:00:00

  • Efficient and long-term intracardiac gene transfer in delta-sarcoglycan-deficiency hamster by adeno-associated virus-2 vectors.

    abstract::Intracardiac gene transfer and gene therapy have been investigated with different vector systems. Here we used adeno-associated virus (AAV) vectors to deliver either a reporter gene or a therapeutic gene into the heart of golden Syrian hamsters. The method of gene delivery was direct infusion of the AAV2 vectors into ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302078

    authors: Li J,Wang D,Qian S,Chen Z,Zhu T,Xiao X

    更新日期:2003-10-01 00:00:00

  • Gene therapy progress and prospects: stem cell plasticity.

    abstract::With the identification of stem cell plasticity several years ago, multiple reports raised hopes that tissue repair by stem cell transplantation could be within reach in the near future. Krause et al reported that a single purified hematopoietic stem cell not only repopulated the bone marrow of a host animal, but also...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/sj.gt.3302571

    authors: Kashofer K,Bonnet D

    更新日期:2005-08-01 00:00:00

  • Robust and prolonged gene expression from injectable polymeric implants.

    abstract::We introduce an injectable system for the formation of a biodegradable DNA-containing implant that releases DNA over a 2-month period to provide a robust and prolonged gene expression at the site. Sustained delivery of the appropriate plasmid DNA resulted in sustained expression of luciferase, the persistent appearanc...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301786

    authors: Eliaz RE,Szoka FC Jr

    更新日期:2002-09-01 00:00:00

  • Liver-directed gene therapy of diabetic rats using an HVJ-E vector containing EBV plasmids expressing insulin and GLUT 2 transporter.

    abstract::Insulin gene therapy in clinical medicine is currently hampered by the inability to regulate insulin secretion in a physiological manner, the inefficiency with which the gene is delivered, and the short duration of gene expression. To address these issues, we injected the liver of streptozotocin-induced diabetic rats ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302644

    authors: Kim YD,Park KG,Morishita R,Kaneda Y,Kim SY,Song DK,Kim HS,Nam CW,Lee HC,Lee KU,Park JY,Kim BW,Kim JG,Lee IK

    更新日期:2006-02-01 00:00:00

  • Regeneration of pancreatic islets in vivo by ultrasound-targeted gene therapy.

    abstract::This study uses a novel approach to gene therapy in which plasmid DNA is targeted to the pancreas in vivo using ultrasound-targeted microbubble destruction (UTMD) to achieve islet regeneration. Intravenous microbubbles carrying plasmids are destroyed within the pancreatic microcirculation by ultrasound, achieving loca...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2010.85

    authors: Chen S,Shimoda M,Wang MY,Ding J,Noguchi H,Matsumoto S,Grayburn PA

    更新日期:2010-11-01 00:00:00

  • Articular cartilage repair by genetically modified bone marrow aspirate in sheep.

    abstract::Bone marrow presents an attractive option for the treatment of articular cartilage defects as it is readily accessible, it contains mesenchymal progenitor cells that can undergo chondrogenic differentiation and, once coagulated, it provides a natural scaffold that contains the cells within the defect. This study was p...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2010.16

    authors: Ivkovic A,Pascher A,Hudetz D,Maticic D,Jelic M,Dickinson S,Loparic M,Haspl M,Windhager R,Pecina M

    更新日期:2010-06-01 00:00:00

  • Genetic co-inactivation of macrophage- and T-tropic HIV-1 chemokine coreceptors CCR-5 and CXCR-4 by intrakines.

    abstract::CC-chemokine receptor (CCR)-5 is the principal coreceptor for the entry of macrophage (M)-tropic HIV-1 viruses into a cell, while CXC-chemokine receptor (CXCR)-4 is the principal coreceptor for T cell line (T)-tropic HIV-1. In this study, we utilized a novel intracellular chemokine (intrakine) strategy to co-inactivat...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300667

    authors: Bai X,Chen JD,Yang AG,Torti F,Chen SY

    更新日期:1998-07-01 00:00:00

  • Defining strategies to extend duration of gene expression from targeted compacted DNA vectors.

    abstract::Gene transfer complexes containing poly-L-lysine (poly-K) and DNA with ligands directed at the serpin enzyme complex receptor (sec-R) deliver reporter genes to receptor-bearing cells in vivo. Expression lasts for about 30 days, when complexes containing long-chain poly-K are used. Extending the duration of expression ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302299

    authors: Ziady AG,Kim J,Colla J,Davis PB

    更新日期:2004-09-01 00:00:00

  • Variegation of retroviral vector gene expression in myeloid cells.

    abstract::We have comparatively evaluated the efficiency of a series of retroviral vectors transducing the gp91-phox gene, whose defects are responsible for impaired production of superoxide anion (O2-) by phagocytic cells and lead to the X-linked form of chronic granulomatous disease (X-CGD). These vectors included four constr...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301057

    authors: Zentilin L,Qin G,Tafuro S,Dinauer MC,Baum C,Giacca M

    更新日期:2000-01-01 00:00:00

  • Human urinary bladder carcinomas express adenovirus attachment and internalization receptors.

    abstract::The use of adenoviral vectors as potent gene delivery systems requires expression of the Coxsackievirus/adenovirus receptor (CVADR) on the target cell surface. This receptor is important for virus attachment to the cell surface. For effective internalization of the vector into the target cell the integrins alpha(v)bet...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301689

    authors: Loskog A,Hedlund T,Wester K,de la Torre M,Philipson L,Malmström PU,Tötterman TH

    更新日期:2002-05-01 00:00:00

  • Towards mutation-independent silencing of genes involved in retinal degeneration by RNA interference.

    abstract::More than one hundred different mutations in the gene encoding rhodopsin are associated with a group of retinal degenerations including retinitis pigmentosa, congenital stationary night blindness and retinitis punctata albescens. Given this large heterogeneity of mutations, it would be ideal to develop mutation-indepe...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302512

    authors: Cashman SM,Binkley EA,Kumar-Singh R

    更新日期:2005-08-01 00:00:00

  • Pre-emptive gene therapy using recombinant adeno-associated virus delivery of extracellular superoxide dismutase protects heart against ischemic reperfusion injury, improves ventricular function and prolongs survival.

    abstract::In high-risk patients, the ideal cardiovascular gene therapy requires a strategy that provides long-term protection of myocardium against episodes of ischemic/reperfusion injury. We report the development of an efficient, long-lasting pre-emptive gene therapy strategy in a rat model of ischemic-reperfusion (I/R) injur...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302250

    authors: Agrawal RS,Muangman S,Layne MD,Melo L,Perrella MA,Lee RT,Zhang L,Lopez-Ilasaca M,Dzau VJ

    更新日期:2004-06-01 00:00:00

  • Efficient central nervous system AAVrh10-mediated intrathecal gene transfer in adult and neonate rats.

    abstract::Intracerebral administration of recombinant adeno-associated vector (AAV) has been performed in several clinical trials. However, delivery into the brain requires multiple injections and is not efficient to target the spinal cord, thus limiting its applications. To assess widespread and less invasive strategies, we te...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2014.121

    authors: Hordeaux J,Dubreil L,Deniaud J,Iacobelli F,Moreau S,Ledevin M,Le Guiner C,Blouin V,Le Duff J,Mendes-Madeira A,Rolling F,Cherel Y,Moullier P,Colle MA

    更新日期:2015-04-01 00:00:00

  • Establishment of complement-resistant retroviral vector by homologous restriction factor 20 gene.

    abstract::Homologous restriction factor 20 (HRF20, CD59) is one of the complement regulatory factors. In this study, the complement-resistant retroviral vector, which possesses the HRF20 gene as a selection gene, was constructed and examined. The virus-producing cell, transduced with complement-resistant retroviral vector, was ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300574

    authors: Hayashi S,Emi N,Okada H,Nagasaka T,Yokoyama I,Takagi H

    更新日期:1998-02-01 00:00:00

  • Gradient of RGD-dependent entry of adenoviral vector in nasal and intrapulmonary epithelia: implications for gene therapy of cystic fibrosis.

    abstract::The efficiency with which adenoviral vectors infect airway epithelial cells in vivo is unclear despite extensive preclinical and clinical studies. Our hypothesis is that gene transfer is limited by vector internalization which is mediated by binding of a fiber with a cellular receptor and the RGD motif of the penton b...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:

    authors: Goldman M,Su Q,Wilson JM

    更新日期:1996-09-01 00:00:00

  • A new plasmid-based microRNA inhibitor system that inhibits microRNA families in transgenic mice and cells: a potential new therapeutic reagent.

    abstract::Current tools for the inhibition of microRNA (miR) function are limited to modified antisense oligonucleotides, sponges and decoy RNA molecules and none have been used to understand miR function during development. CRISPR/Cas-mediated deletion of miR sequences within the genome requires multiple chromosomal deletions ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2016.22

    authors: Cao H,Yu W,Li X,Wang J,Gao S,Holton NE,Eliason S,Sharp T,Amendt BA

    更新日期:2016-06-01 00:00:00

  • In vivo targeted gene transfer into liver cells mediated by a novel galactosyl-D-lysine/D-serine copolymer.

    abstract::A novel synthetic polypeptide designed as a DNA binding-molecule for liver-specific, receptor-mediated, gene transfer was used to selectively introduce reporter genes into liver cells in the form of plasmid DNA-ligand complexes. The polypeptide was a D-lysine/D-serine copolymer (Lys/Ser = 33/36 or 53/60) modified with...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300868

    authors: Hisayasu S,Miyauchi M,Akiyama K,Gotoh T,Satoh S,Shimada T

    更新日期:1999-04-01 00:00:00

  • Gene therapy in transplantation in the year 2000: moving towards clinical applications?

    abstract::Transplantation faces several major obstacles that could be overcome by expression of immunomodulatory proteins through application of gene therapy techniques. Gene therapy strategies to prolong graft survival involve gene transfer of immunosuppressive or graft-protecting molecules. Very promising results have been ob...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/sj.gt.3301083

    authors: Guillot C,Le Mauff B,Cuturi MC,Anegon I

    更新日期:2000-01-01 00:00:00

  • Activated polyamidoamine dendrimers, a non-viral vector for gene transfer to the corneal endothelium.

    abstract::We investigated the efficiency of activated polyamidoamine dendrimers, a new class of nonviral vectors, to transfect rabbit and human corneas in ex vivo culture. In addition to assessing the expression of a marker gene we have demonstrated that this approach can be used to induce the production of TNF receptor fusion ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300886

    authors: Hudde T,Rayner SA,Comer RM,Weber M,Isaacs JD,Waldmann H,Larkin DF,George AJ

    更新日期:1999-05-01 00:00:00