Effect of immunity on gene delivery into anterior horn motor neurons by live attenuated herpes simplex virus vector

Kamiyama, Hironaga; Kurimoto, Masanori; Yamamura, Jun-ichi; Uwano, Teruko; Hirashima, Yutaka; Kurokawa, Mineo; Endo, Shunro; Shiraki, Kimíyasu

doi:10.1038/sj.gt.3301503

Cited by 5 publications

(8 citation statements)

References 54 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The lungs of infected mice were removed under anesthesia from at least 3 mice in each group on days 1 and 2 p.i. and fixed for hematoxylin and eosin staining or rapidly frozen in liquid nitrogen for immunohistochemical examination as described previously (Imakita et al, 2000;Kamiyama et al, 2001;Fukuda et al, 2003). Briefly, 6 µm thick serial sections of the frozen lungs were dried at room temperature, fixed with cold acetone, and then washed with TBS.…”

Section: Methodsmentioning

confidence: 99%

“…Mice were perfused with 0.1 mo/l phosphate buffer (pH 7.4) containing 4% paraformaldehyde and the lungs were rapidly frozen in liquid nitrogen as described by Kamiyama et al (2001). Briefly, the frozen sections (6 µm thick) were fixed with 4% paraformaldehyde in PBS and were treated with 0.2% Triton-X 100 and 10 µg/ml proteinase K. They were again fixed with 4% paraformaldehyde and immersed in 2 mg/ml glycine sequentially dehydrated with ethanol and dried.…”

Section: Methodsmentioning

confidence: 99%

“…The digoxigenin-labeled murine IL-12 p40 DNA probe was generated as a 497-bp fragment by PCR using a DIG DNA Labeling Mix (Roche) with the forward primer 5'-TCTCT-GTCTGCAGAGAAGGTCACACTGGAC-3' and reverse primer 5'-CTAGGATCGGACCCTGCAGGGAACA ATGC-3'. The sections were pre-hybridized with 50% formamide in 5x SSC and then hybridized with denatured digoxigenin-labeled probes at 46°C overnight (Kamiyama et al, 2001;Fukuda et al, 2003). To detect bound digoxigenin-labeled probes, the sections were blocked with blocking solution [1% blocking buffer (Roche Applied Science), 0.1% Triton-X 100 in 0.1 mol/l Tris-HCl, 0.15 mol/l NaCl (pH 7.5)] at room temperature for 30 mins.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Interleukin 12 is a primary cytokine responding to influenza virus infection in the respiratory tract of mice

Hama

Kurokawa²,

Imakita³

et al. 2009

View full text Add to dashboard Cite

. Abbreviations: BALF = bronchoalveolar lavage fluid; IFN = interferon; IL = interleukin; i.n. = intranasal; MAb(s) = monoclonal antibody(ies); p.i. = post infection; TNF = tumor necrosis factor Interleukin 12 is a primary cytokine responding to influenza virus infection in the respiratory tract of mice Summary. -We have reported previously that an increase in interleukin 12 (IL-12) production in the lungs of mice infected with Influenza A virus or an intranasal (i.n.) administration of IL-12 to the infected mice alleviated pneumonia (Tsurita et al., J. Pharmacol. Exp. Therapeut. 298, 362-368, 2001). In this study, we found that in the bronchoalveolar lavage fluids (BALF) obtained from mice infected i.n. with Influenza A virus IL-12 was elevated on day 1 post infection (p.i.) and was followed by tumor necrosis factor α (TNF-α), IL-18, and interferons α, β, and γ (IFN-α, -β, and -γ) on day 2 p.i. Histochemical analyses of the infected lungs on day 1 p.i. showed the presence of IL-12 and IL-12 mRNA in mononuclear and macrophage-like cells and colocalization of macrophages with viral antigen, while other cytokines were absent. Thus, IL-12 was produced by macrophages infiltrating the infected epithelium as the first response cytokine and its production at the site of infection may direct an early immune defense to alleviate the severity of infection.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Interleukin 12 is a primary cytokine responding to influenza virus infection in the respiratory tract of mice

Hama

Kurokawa²,

Imakita³

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Tumor nodules were removed on day 3, 7, 10, or 14 after HSV inoculation, fixed with 4% paraformaldehyde in PBS at 4°C overnight, dehydrated with increasing concentrations of ethanol, embedded in paraffin, and cut into 4 µm sections. 29,30) The sections were stained with standard hematoxylin and eosin, and immunostained with the following primary antibody: GK1.5 rat anti-mouse CD4 monoclonal antibody, 53-6.7 rat anti-mouse CD8a monoclonal antibody, PK136 mouse anti-mouse NK1.1 monoclonal antibody (PharMingen, San Diego, CA), Ki-1 mouse anti-human CD30 monoclonal antibody, MOMA-2 rat anti-mouse macrophage monoclonal antibody (Immunotech, Marseilles Cedex, France), IE8-G6 mouse anti-human TNF-α monoclonal antibody, H-5 mouse anti-human TNF-R1 monoclonal antibody, APO-1 mouse anti-human FAS monoclonal antibody, NOK-1 mouse anti-human FAS-L monoclonal antibody (Santa Cruz Biotechnology, Inc., Santa Cruz, CA) or rabbit anti-HSV type 1 polyclonal antibody (Dako Laboratories, Glostrup, Denmark). Reacted antibody was detected with a DAKO LSAB2 Kit/HRP (Dako Laboratories).…”

Section: Methodsmentioning

confidence: 99%

“…A live, attenuated HSV type 1 strain, βH1, expressing β-galactosidase and its parent, HF, and wild 7401H strains were prepared in Vero cells as described previously. [27][28][29][30] Animals. Four-week-old male athymic BALB/c nu/nu mice (Japan SLC, Inc., Shizuoka, Japan) were housed in sterile cages.…”

Section: Methodsmentioning

confidence: 99%

Herpes simplex virus‐induced, death receptor‐dependent apoptosis and regression of transplanted human cancers

et al. 2004

View full text Add to dashboard Cite

he use of replication-competent viral vectors, in particular herpes simplex virus (HSV) type 1 vectors, is a promising strategy for cancer therapy because the virus can replicate and spread in situ, exhibiting oncolytic activity through a direct cytopathic effect.1) A number of oncolytic HSV vectors have been developed by introduction of mutations that disrupt genes associated with neurovirulence and/or viral DNA synthesis in order to restrict viral replication in transformed cells and to diminish the infectious disease.2-11) Restriction of viral growth by introduction of a tissue-specific calponin promoter into the HSV genome resulted in efficient oncolysis of malignant soft tissue and bone tumors.12) Evidence to date following administration of such vectors into the brain attests to their safety, an important observation in light of the neuropathogenicity of the virus. Phase 1 clinical trials of these vectors are either ongoing or completed, without any severe adverse events.13-16) These variants have been demonstrated to be effective in the treatment of a wide variety of malignancies including brain, breast, colorectal, prostate, head and neck cancers, disseminated peritoneal, and soft tissue and bone tumors in animal models. 12,[17][18][19][20][21][22] On the basis of early studies using immunocompromised athymic or severe combined immunodeficiency mice, one mechanism of antitumor activity of oncolytic HSV is thought to be tumor cell destruction due to virus infection and intracellular replication.Recent studies in immunocompetent syngeneic models have suggested that the host defense mechanisms provoked by HSV play important roles in oncolysis. Oncolytic HSV growing within a tumor elicits an immune response to HSV and tumorspecific antigens.23) Colon cancer tumors were transplanted on the bilateral flanks of syngeneic immunocompetent mice, and HSV was inoculated into one of the established tumors. The tumors in the syngeneic immunocompetent mice showed greater and prompter regression than those in athymic animals. Further, the inoculation into a tumor on one side induced regression of the tumor on the other side. In addition, a CD8 + T cell-mediated response is generated to a tumor-specific antigen on the cells. The recognition that conditionally replicating HSV vectors induce antitumor immune responses has led to engineering of HSV to carry genes for cytokines that potentiate the antitumor immune response. 11,[24][25][26] We examined the antitumor effect of an attenuated HSV expressing β-galactosidase, βH1, using immunocompromised athymic models to analyze the direct effect of HSV on oncolysis in the absence of an antitumor immune response. We found that tumor regression due to HSV was mediated by apoptosis that occurred during HSV growth and subsequent expression of CD30, CD30 ligand (CD30L), tumor necrosis factor (TNF)-α, TNF-receptor 1 (TNF-R1), FAS, and FAS-L in transplanted human cancer cells. These observations suggest that expression of these ligands and receptors might enhance the susceptibility of ...

show abstract

Influence of the Immune System on Central Nervous System Gene Transfer

Forsayeth¹

2006

Gene Therapy of the Central Nervous System

View full text Add to dashboard Cite

Effect of immunity on gene delivery into anterior horn motor neurons by live attenuated herpes simplex virus vector

Cited by 5 publications

References 54 publications

Interleukin 12 is a primary cytokine responding to influenza virus infection in the respiratory tract of mice

Interleukin 12 is a primary cytokine responding to influenza virus infection in the respiratory tract of mice

Herpes simplex virus‐induced, death receptor‐dependent apoptosis and regression of transplanted human cancers

Influence of the Immune System on Central Nervous System Gene Transfer

Contact Info

Product

Resources

About