Adenovirus-Mediated Gene Transfer of Interleukin-4 to Corneal Endothelial Cells and Organ Cultured Corneas Leads to High IL-4 Expression

Ritter, Thomas; Vogt, Katrin; Rieck, Peter; Schilling-Schön, Antje; Kolls, Jay K.; Hartmann, Christian; Volk, Hans‐Dieter; Pleyer, Uwe

doi:10.1006/exer.1999.0731

Cited by 35 publications

(31 citation statements)

References 21 publications

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“…The AdBcl-xL and AdNull adenoviral vectors were generated, propagated and purified as described before (Fallaux et al, 1996;Ritter et al, 1999). The AdshRNA-C9 and AdshRNA-eGFP vectors were generated using the ViraPower adenovirus expression system (Invitrogen).…”

Section: Adenoviral Vector Production and Transductionmentioning

confidence: 99%

A non-apoptotic role for caspase-9 in muscle differentiation

Murray

McMahon

Howley

et al. 2008

Journal of Cell Science

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155

117

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Caspases, a family of cysteine proteases most often investigated for their roles in apoptosis, have also been demonstrated to have functions that are vital for the efficient execution of cell differentiation. One such role that has been described is the requirement of caspase-3 for the differentiation of skeletal myoblasts into myotubes but, as yet, the mechanism leading to caspase-3 activation in this case remains elusive. Here, we demonstrate that caspase-9, an initiator caspase in the mitochondrial death pathway, is responsible for the activation of caspase-3 in differentiating C2C12 cells. Reduction of caspase-9 levels, using an shRNA construct, prevented caspase-3 activation and inhibited myoblast fusion. Myosin-heavychain expression, which accompanies myoblastic differentiation, was not caspase-dependent. Overexpression of Bcl-xL, a protein that inhibits caspase-9 activation, had the same effect on muscle differentiation as knockdown of caspase-9. These data suggest that the mitochondrial pathway is required for differentiation; however, the release of cytochrome c or Smac (Diablo) could not be detected, raising the possibility of a novel mechanism of caspase-9 activation during muscle differentiation.

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Section: Adenoviral Vector Production and Transductionmentioning

confidence: 99%

A non-apoptotic role for caspase-9 in muscle differentiation

Murray

McMahon

Howley

et al. 2008

Journal of Cell Science

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155

117

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“…The generation of recombinant E1-deleted replicationincompetent adenovirus type 5 vectors carrying the genes encoding β−galactosidase (Adβ-Gal) and rat IL-4 (AdrIL-4), respectively, has been described elsewhere [18,19]. Primary PSC activated by in vitro cultivation for 7 to 10 days after isolation from rat pancreas were used as target cells.…”

Section: Adenovirus Vectors and Cell Transductionmentioning

confidence: 99%

Adenovirus-mediated gene transfer of interleukin-4 into pancreatic stellate cells promotes interleukin-10 expression

Brock

Sparmann

Ritter

et al. 2006

Journal of Cellular and Molecular Medicine

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Pancreatic stellate cells (PSC) are crucially involved in the development of fibrosis, a hallmark of chronic pancreatitis. Therefore, PSC represent an attractive target for the modulation of cellular functions providing the prerequisite for the establishment of novel therapeutic strategies like transfer of genetic material to the cells. Based on recent studies suggesting that the chronic course of pancreatitis is associated with immune deviation towards a Th1 cytokine profile, we have investigated the applicability of primary PSC to an adenovirus-mediated transfer of the cDNA encoding the Th2 cytokine interleukin (IL) 4 and the autocrine-acting effects of IL 4 on the cells in vitro. The trans-duction of primary PSC with a replication-incompetent adenovirus type 5 vector carrying the cDNA encoding rat IL-4 resulted in a distinct expression of the cytokine on mRNA and protein level for two weeks. Similar to recombinant IL 4, effects of the endogenously synthesized cytokine were mediated by the signal transducer and activator of transcription (STAT)6. Interestingly, beside the increase of PSC proliferation, IL 4 transduction was accompanied by an up-regulation in the endogenous expression of the anti-inflammatory cytokine IL 10. In summary, our data suggest that PSC are suitable targets for gene therapy modulating cellular interactions in the pancreas.

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“…As the main target of corneal allograft rejection [11], corneal endothelial cells are more suitable than other corneal cell types for cytokine gene transfer studies. Previously, gene transfer to corneal endothelium using recombinant adenovirus (Ad) has been described [12][13][14][15]. However, the widely used Ad vectors have several undesired side-effects, and immunestimulating properties of the virus may limit the benefits of recombinant Ad for purposes of immune suppression [16].…”

Section: Introductionmentioning

confidence: 99%

Efficiency of Cytokine Gene Transfer in Corneal Endothelial Cells and Organ-Cultured Corneas Mediated by Liposomal Vehicles and Recombinant Adenovirus

Bertelmann

Ritter²,

Vogt³

et al. 2003

Ophthalmic Res

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Purpose: Gene transfer of immunoregulatory cytokines could contribute to reduce rejection of corneal grafts. The aim of our study was to examine the gene transfer efficiency of liposomal vehicles compared to adenoviral vectors for transferring the Epstein-Barr-virus-derived interleukin 10 homologue (viral IL-10, vIL-10) into corneal endothelial cells and organ-cultured human corneas (HC) in vitro. Method: To test liposomal efficiency, 2 lipid formulations (SP-Chol/DOPE 20/80 and DDAB/DOPE 30/70 in various concentrations) were complexed with a plasmid containing the vIL-10 cDNA in an eukaryotic expression vector (pcDSRα-BCRF-I). The complexes were transferred to (1) subconfluent bovine corneal endothelial cells (BCEC) after 1 passage and to (2) HC stored in organ culture. In addition, BCEC and HC were transduced with the recombinant adenoviral vector encoding for vIL-10 (AdvIL-10). Secretion of vIL-10 in the supernatants from both transfected BCEC and HC was measured by specific ELISA. Results: For gene transfer in BCEC, both transfection methods (liposomes and adenovirus) led to high secretion of vIL-10 [>2 ng/ml (liposomes) and <150 ng/ml (adenovirus) per 5,000 initially planted BCEC]. Expression levels in BCEC were dependent on the concentration of applied liposomes. For gene transfer in HC, only the adenoviral transduction technique achieved a high production of vIL-10, whereas liposomal transfection led only to low vIL-10 secretion (4.8 µg/ml vs. 95 pg/ml per quarter of cornea). Conclusion: For transfection of corneal endothelial cells in culture, liposomes can be considered as a safe and useful alternative method of gene transfer avoiding side-effects of viral vectors. However, for transfection of organ-cultured HC, adenoviral vectors are superior to liposomal vehicles.

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Adenovirus-Mediated Gene Transfer of Interleukin-4 to Corneal Endothelial Cells and Organ Cultured Corneas Leads to High IL-4 Expression

Cited by 35 publications

References 21 publications

A non-apoptotic role for caspase-9 in muscle differentiation

A non-apoptotic role for caspase-9 in muscle differentiation

Adenovirus-mediated gene transfer of interleukin-4 into pancreatic stellate cells promotes interleukin-10 expression

Efficiency of Cytokine Gene Transfer in Corneal Endothelial Cells and Organ-Cultured Corneas Mediated by Liposomal Vehicles and Recombinant Adenovirus

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