Gene silencing of NALP3 protects against liver ischemia-reperfusion injury in mice.


:Liver ischemia-reperfusion (I/R) injury is a multifactorial process that affects graft function after liver transplantation. Inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-18, have been shown to play key roles in the pathophysiology of liver I/R injury. Studies have indicated that NALP3 (NACHT domain, leucine-rich repeat [LRR] domain, and pyrin domain [PYD]-containing protein-3) inflammasome is pivotal in the processing and releasing of IL-1β and IL-18. The aim of this study was to test whether NALP3 silencing has a protective effect in murine liver I/R injury. Using a partial lobar liver warm ischemia model, mice were hydrodynamically injected with pNALP3shRNA, pshRNANC, or saline 48 hr before ischemia. Those mice pretreated with pNALP3shRNA showed decreased serum alanine aminotransferase levels; inhibited production of proinflammatory cytokines such as IL-1β, IL-18, TNF-α, and IL-6 by downregulation of caspase-1 activation and NF-κB activity; as well as decreased release of HMGB1 (high-mobility group box-1) and inflammatory cell infiltration, leading to the prevention of liver I/R injury, when compared with controls. Histology revealed that pretreatment with pNALP3shRNA significantly ameliorated hepatocellular damage after I/R. Thus, by using a small hairpin RNA approach, our study confirms that NALP3 signaling is involved in liver I/R and that silencing of NALP3 can protect the liver from I/R injury by reducing IL-1β, IL-18, TNF-α, IL-6, and HMGB1 release through downregulation of caspase-1 activation and NF-κB activity.


Hum Gene Ther


Human gene therapy


Zhu P,Duan L,Chen J,Xiong A,Xu Q,Zhang H,Zheng F,Tan Z,Gong F,Fang M




Has Abstract


2011-07-01 00:00:00












  • Adenovirus-based vaccines for fighting infectious diseases and cancer: progress in the field.

    abstract::The field of adenovirology is undergoing rapid change in response to increasing appreciation of the potential advantages of adenoviruses as the basis for new vaccines and as vectors for gene and cancer therapy. Substantial knowledge and understanding of adenoviruses at a molecular level has made their manipulation for...

    journal_title:Human gene therapy

    pub_type: 杂志文章,评审


    authors: Majhen D,Calderon H,Chandra N,Fajardo CA,Rajan A,Alemany R,Custers J

    更新日期:2014-04-01 00:00:00

  • Oncolytic measles virus encoding thyroidal sodium iodide symporter for squamous cell cancer of the head and neck radiovirotherapy.

    abstract::Oncolytic measles virus (MV) encoding the human thyroidal sodium iodide symporter (MV-NIS) has proved to be safe after intraperitoneal or intravenous administration in patients with ovarian cancer or multiple myeloma, respectively, but it has not yet been administered through intratumoral injection in humans. Squamous...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Li H,Peng KW,Russell SJ

    更新日期:2012-03-01 00:00:00

  • Engineered U7 Small Nuclear RNA Restores Correct β-Globin Pre-mRNA Splicing in Mouse βIVS2-654-Thalassemic Erythroid Progenitor Cells.

    abstract::Restoration of correct splicing of βIVS2-654-globin pre-mRNA was previously accomplished in erythroid cells from β-thalassemia/HbE patients by an engineered U7 small nuclear RNA (snRNA) that carried a sequence targeted to the cryptic branch point and an exonic splicing enhancer, U7.BP+623 snRNA. In this study, this ap...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: d'Arqom A,Nualkaew T,Jearawiriyapaisarn N,Kole R,Svasti S

    更新日期:2020-11-02 00:00:00

  • Gene transfer of adenosine deaminase into primitive human hematopoietic progenitor cells.

    abstract::The inherited deficiency in adenosine deaminase (ADA), which results in severe combined immunodeficiency, is generally regarded as an optimal model for the development of human somatic gene therapy. The ideal target for the correction of ADA deficiency and other lympho-hematopoietic disorders would be the hematopoieti...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Cournoyer D,Scarpa M,Mitani K,Moore KA,Markowitz D,Bank A,Belmont JW,Caskey CT

    更新日期:1991-10-01 00:00:00

  • Quantification and characterization of autotransduction in retroviral vector producer cells.

    abstract::Gene therapy has evolved into a tempting strategy for the management of cancer and other life-threatening diseases. Various approaches employ retroviral vectors to deliver the therapeutic gene. The profound knowledge about retrovirus biology allows the generation of increasingly advanced vector systems as well as an a...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Brandtner EM,Kodajova P,Knapp E,Ertl R,Tabotta W,Salmons B,Günzburg WH,Hohenadl C

    更新日期:2008-01-01 00:00:00

  • Using a tropism-modified adenoviral vector to circumvent inhibitory factors in ascites fluid.

    abstract::Peritoneal compartmentalization of advanced stage ovarian cancer provides a rational scenario for gene therapy strategies. Several groups are exploring intraperitoneal administration of adenoviral (Ad) vectors for this purpose. We examined in vitro gene transfer in the presence of ascites fluid from ovarian cancer pat...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Blackwell JL,Li H,Gomez-Navarro J,Dmitriev I,Krasnykh V,Richter CA,Shaw DR,Alvarez RD,Curiel DT,Strong TV

    更新日期:2000-08-10 00:00:00

  • Fibroblast growth factor 2-retargeted adenoviral vectors exhibit a modified biolocalization pattern and display reduced toxicity relative to native adenoviral vectors.

    abstract::Targeted vectors provide a number of advantages for systemic and local gene delivery strategies. Several groups have investigated the utility of using various ligands to alter the tropism of adenovirus (Ad) vectors. We have previously demonstrated that fibroblast growth factor (FGF) ligands can specifically target DNA...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Printz MA,Gonzalez AM,Cunningham M,Gu DL,Ong M,Pierce GF,Aukerman SL

    更新日期:2000-01-01 00:00:00

  • Enhancing Graduate and Postdoctoral Education To Create a Sustainable Biomedical Workforce.

    abstract::PhD-trained biomedical scientists are moving into an increasingly diverse variety of careers within the sciences. However, graduate and postdoctoral training programs have historically focused on academic career preparation, and have not sufficiently prepared trainees for transitioning into other scientific careers. A...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Fuhrmann CN

    更新日期:2016-11-01 00:00:00

  • Selective killing of AFP-positive hepatocellular carcinoma cells by adeno-associated virus transfer of the herpes simplex virus thymidine kinase gene.

    abstract::The use of viral thymidine kinase (TK) gene coupled with the administration of ganciclovir to render cancer cell death has been studied extensively. Many of these experiments utilized retrovirus to transfer the TK gene under the control of a nonspecific promoter. Because nonspecific expression of the viral TK gene may...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Su H,Chang JC,Xu SM,Kan YW

    更新日期:1996-03-01 00:00:00

  • Inhibitory effect of nuclear factor-κB decoy oligodeoxynucleotide on liver fibrosis through regulation of the epithelial-mesenchymal transition.

    abstract::The epithelial-mesenchymal transition (EMT) has been recognized to occur during embryonic development, fibrosis, and tumor metastasis. Nuclear factor (NF)-κB plays a central role in mediating the inflammation and wound-healing responses during liver fibrogenesis. However, the involvement of NF-κB during EMT in liver c...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Kim KH,Lee WR,Kang YN,Chang YC,Park KK

    更新日期:2014-08-01 00:00:00

  • Gene expression following direct injection of DNA into liver.

    abstract::The liver is an attractive target tissue for gene therapy. Current approaches for hepatic gene delivery include retroviral and adenoviral vectors, liposome/DNA, and peptide/DNA complexes. This study describes a technique for direct injection of DNA into liver that led to significant gene expression. Gene expression wa...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Hickman MA,Malone RW,Lehmann-Bruinsma K,Sih TR,Knoell D,Szoka FC,Walzem R,Carlson DM,Powell JS

    更新日期:1994-12-01 00:00:00

  • Complete regression of large solid tumors using engineered drug-resistant hematopoietic cells and anti-CD137 immunotherapy.

    abstract::Combining chemotherapy and immunotherapy is problematic because chemotherapy can ablate the immune responses initiated by modulators of the immune system. We hypothesized that protection of immunocompetent cells from the toxic effects of chemotherapy, using drug resistance gene therapy strategies, would allow the comb...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: McMillin DW,Hewes B,Gangadharan B,Archer DR,Mittler RS,Spencer HT

    更新日期:2006-08-01 00:00:00

  • Myoblast gene therapy in canine mucopolysaccharidosis. I: Abrogation by an immune response to alpha-L-iduronidase.

    abstract::Three dogs with deficiency of the lysosomal enzyme alpha-L-iduronidase were treated by gene replacement therapy targeted at muscle. Direct intramuscular injections of plasmid encoding the alpha-L-iduronidase gene cDNA resulted in no detectable enzyme production, but may have resulted in immunologic sensitization to id...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Shull RM,Lu X,McEntee MF,Bright RM,Pepper KA,Kohn DB

    更新日期:1996-08-20 00:00:00

  • Inhibition of human immunodeficiency virus replication and growth advantage of CD4+ T cells from HIV-infected individuals that express intracellular antibodies against HIV-1 gp120 or Tat.

    abstract::Current clinical gene therapy protocols for the treatment of human immunodeficiency virus type 1 (HIV-1) infection often involve the ex vivo transduction and expansion of CD4+ T cells derived from HIV-positive patients at a late stage in their disease (CD4 count <400). These protocols involve the transduction of T cel...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Poznansky MC,Foxall R,Mhashilkar A,Coker R,Jones S,Ramstedt U,Marasco W

    更新日期:1998-03-01 00:00:00

  • In vivo targeting of tumor endothelial cells by systemic delivery of lentiviral vectors.

    abstract::Tumor angiogenesis is a rate-limiting factor for tumor growth, and the endothelial cells of tumor vessels display specific features that can be exploited for the selective delivery of cancer therapeutics. To specifically target exogenous genes to angiogenic tumor vessels, we generated a panel of vesicular stomatitis v...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: De Palma M,Venneri MA,Naldini L

    更新日期:2003-08-10 00:00:00

  • Systemic Correction of Murine Glycogen Storage Disease Type IV by an AAV-Mediated Gene Therapy.

    abstract::Deficiency of glycogen branching enzyme (GBE) causes glycogen storage disease type IV (GSD IV), which is characterized by the accumulation of a less branched, poorly soluble form of glycogen called polyglucosan (PG) in multiple tissues. This study evaluates the efficacy of gene therapy with an adeno-associated viral (...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Yi H,Zhang Q,Brooks ED,Yang C,Thurberg BL,Kishnani PS,Sun B

    更新日期:2017-03-01 00:00:00

  • hMaxi-K gene transfer in males with erectile dysfunction: results of the first human trial.

    abstract::Eleven patients with moderate to severe erectile dysfunction (ED) were given a single-dose corpus cavernosum injection of hMaxi-K, a "naked" DNA plasmid carrying the human cDNA encoding hSlo (for human slow-poke), the gene for the alpha, or pore-forming, subunit of the human smooth muscle Maxi-K channel. Three patient...

    journal_title:Human gene therapy

    pub_type: 杂志文章,多中心研究


    authors: Melman A,Bar-Chama N,McCullough A,Davies K,Christ G

    更新日期:2006-12-01 00:00:00

  • Upregulation of Bag-1 by ex vivo gene transfer protects rat livers from ischemia/reperfusion injury.

    abstract::Bag-1 exerts powerful antiapoptotic effects by binding and stabilizing Bcl-2 and interacting with the tumor necrosis factor receptor type I-induced death signal. We examined the effects of overexpression of Bag-1 by ex vivo adenoviral gene transfer on cold (4 degrees C for 24 hr) ischemia/reperfusion (I/R) injury of r...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Sawitzki B,Amersi F,Ritter T,Fisser M,Shen XD,Ke B,Busuttil R,Volk HD,Kupiec-Weglinski JW

    更新日期:2002-08-10 00:00:00

  • Transient expression of genes transferred in vivo into heart using first-generation adenoviral vectors: role of the immune response.

    abstract::Gene therapy for heart diseases requires availability of an efficient vector for gene transfer into myocardium. Recombinant adenovirus expressing the Escherichia coli beta-galactosidase (beta-Gal) gene was shown to infect rat cardiocytes efficiently in vivo. However, a time course of gene expression showed that transg...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Gilgenkrantz H,Duboc D,Juillard V,Couton D,Pavirani A,Guillet JG,Briand P,Kahn A

    更新日期:1995-10-01 00:00:00

  • Differentiation and expansion of lentivirus vector-marked dendritic cells derived from human CD34(+) cells.

    abstract::The in vitro genetic manipulation of dendritic cells (DCs) for the expression of foreign proteins or peptides will assist in the development of immunotherapeutic approaches to treat cancer, immunological disorders, and/or infectious diseases. Reports have shown the expansion and differentiation of CD34(+) progenitor c...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Evans JT,Cravens P,Lipsky PE,Garcia JV

    更新日期:2000-12-10 00:00:00

  • Rescue of Adeno-Associated Virus Production by shRNA Cotransfection.

    abstract::Adeno-associated virus (AAV) vector technology is rapidly advancing and becoming not only the leading vector platform in the field of gene therapy but also a useful tool for functional genomic studies of novel proteins. As most vectors utilize constitutive promoters, this results in transgene expression during product...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Guimaro MC,Afione SA,Tanaka T,Chiorini JA

    更新日期:2020-10-01 00:00:00

  • Long-term efficacy after [E1-, polymerase-] adenovirus-mediated transfer of human acid-alpha-glucosidase gene into glycogen storage disease type II knockout mice.

    abstract::Glycogen storage disease type II (GSD-II) is a lethal, autosomal recessive metabolic myopathy caused by a lack of acid-alpha-glucosidase (GAA) activity in the cardiac and skeletal muscles. Absence of adequate intralysosomal GAA activity results in massive amounts of glycogen accumulation in multiple muscle groups, res...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Ding EY,Hodges BL,Hu H,McVie-Wylie AJ,Serra D,Migone FK,Pressley D,Chen YT,Amalfitano A

    更新日期:2001-05-20 00:00:00

  • Engineered zinc-finger proteins can compensate genetic haploinsufficiency by transcriptional activation of the wild-type allele: application to Willams-Beuren syndrome and supravalvular aortic stenosis.

    abstract::Williams-Beuren syndrome (WBS) and supravalvular aortic stenosis (SVAS) are genetic syndromes marked by the propensity to develop severe vascular stenoses. Vascular lesions in both syndromes are caused by haploinsufficiency of the elastin gene. We used these distinct genetic syndromes as models to evaluate the feasibi...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Zhang P,Huang A,Morales-Ruiz M,Starcher BC,Huang Y,Sessa WC,Niklason LE,Giordano FJ

    更新日期:2012-11-01 00:00:00

  • Capsid-modified adenoviral vectors for improved muscle-directed gene therapy.

    abstract::Skeletal muscle represents an attractive target tissue for adenoviral gene therapy to treat muscle disorders and as a production platform for systemic expression of therapeutic proteins. However, adenovirus serotype 5 vectors do not efficiently transduce adult muscle tissue. Here we evaluated whether capsid modificati...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Guse K,Suzuki M,Sule G,Bertin TK,Tyynismaa H,Ahola-Erkkilä S,Palmer D,Suomalainen A,Ng P,Cerullo V,Hemminki A,Lee B

    更新日期:2012-10-01 00:00:00

  • Interleukin-2 gene transduction into freshly isolated lung adenocarcinoma cells with adenoviral vectors.

    abstract::We evaluated the efficiency of gene transduction and of gene expression by adenoviral vectors in human lung adenocarcinoma cells. Freshly isolated cancer cells were collected from pleural effusions in adenocarcinoma patients by centrifugation with a Percoll gradient. Adenoviral vectors resulted in effective gene trans...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Heike Y,Takahashi M,Kanegae Y,Sato Y,Saito I,Saijo N

    更新日期:1997-01-01 00:00:00

  • Early interaction of adeno-associated virus serotype 8 vector with the host immune system following intramuscular delivery results in weak but detectable lymphocyte and dendritic cell transduction.

    abstract::Following in vivo recombinant adeno-associated virus (rAAV)-based gene transfer, adaptive immune responses specific to the vector or the transgene product have emerged as a potential roadblock to successful clinical translation. The occurrence of such responses depends on several parameters, including the route of vec...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Gernoux G,Guilbaud M,Dubreil L,Larcher T,Babarit C,Ledevin M,Jaulin N,Planel P,Moullier P,Adjali O

    更新日期:2015-01-01 00:00:00

  • Improved titers of retroviral vectors from the human FLYRD18 packaging cell line in serum- and protein-free medium.

    abstract::The influence of serum on the production of retroviral vectors by the HT1080 human fibrosarcoma-derived packaging cell line FLYRD18 was investigated. A fourfold increase in virus titer was observed under serum-free conditions, as compared with medium supplemented with 10% fetal calf serum. A similar improvement was al...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Gerin PA,Gilligan MG,Searle PF,Al-Rubeai M

    更新日期:1999-08-10 00:00:00

  • Antisense oligonucleotides for the treatment of spinal muscular atrophy.

    abstract::Spinal muscular atrophy (SMA) is an autosomal recessive disease affecting ∼1 in 10,000 live births. The most striking component is the loss of α-motor neurons in the ventral horn of the spinal cord, resulting in progressive paralysis and eventually premature death. There is no current treatment paradigm other than sup...

    journal_title:Human gene therapy

    pub_type: 杂志文章,评审


    authors: Porensky PN,Burghes AH

    更新日期:2013-05-01 00:00:00

  • Recombinant adeno-associated virus vectors efficiently and persistently transduce chondrocytes in normal and osteoarthritic human articular cartilage.

    abstract::Successful gene transfer into articular cartilage is a prerequisite for gene therapy of articular joint disorders. In the present study we tested the hypothesis that recombinant adeno-associated virus (rAAV) vectors are capable of effecting gene transfer in isolated articular chondrocytes in vitro, articular cartilage...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Madry H,Cucchiarini M,Terwilliger EF,Trippel SB

    更新日期:2003-03-01 00:00:00

  • Induction of transgene-specific cytotoxic T lymphocyte responses after transplantation of gene-modified CD34+ cells despite nonablative immunosuppressive conditioning.

    abstract::In previous studies we showed that low-dose irradiation and immunosuppression with cyclosporine and mycophenolate mofetil prolonged in vivo persistence of gene-modified T cells but was unable to induce tolerance. We hypothesized that the lack of sustained antigen presentation because of the limited life span of the in...

    journal_title:Human gene therapy

    pub_type: 杂志文章


    authors: Piasecki JC,Beagles K,Beard BC,Riddell S,Kiem HP

    更新日期:2008-01-01 00:00:00