Intrasplenic electro-transfer of IL-4 encoding plasmid DNA efficiently inhibits rat experimental allergic encephalomyelitis

Ho, Seong-Hyun; Lee, Hwang-Jae; Kim, Joo Young; Jeong, Jae-Gyun; Kim, Sujeong; Yu, Seung Shin; Jin, Zhe; Kim, Sun‐Young; Kim, Jong-Mook

doi:10.1016/j.bbrc.2006.03.030

Cited by 11 publications

(6 citation statements)

References 35 publications

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“…However, the link between IL-4 responses and proinflammatory IL-12 production through 12/15-LO is consistent with the observation that transgenic NOD mice expressing high levels of IL-4 under the control of the rat insulin promoter actually show increased inflammation and enhancement of islet-specific effector T-cell function (48). IL-4 does appear to decrease the severity of experimental allergic encephalomyelitis (EAE), a rodent model of multiple sclerosis (49), possibly accounting for the report that deletion of 12/15-LO exacerbates EAE in mice (50). We speculate that the protective action of 12/15-LO in the NOD mouse model of type 1 diabetes is due to the important role of IL-12 in type 1 diabetes, in contrast to the critical role of IL-23 (and not IL-12) for the induction of EAE (51).…”

Section: Discussionmentioning

confidence: 49%

Nonobese Diabetic (NOD) Mice Congenic for a Targeted Deletion of 12/15-Lipoxygenase Are Protected From Autoimmune Diabetes

et al. 2008

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OBJECTIVE-12/15-lipoxygenase (12/15-LO), one of a family of fatty acid oxidoreductase enzymes, reacts with polyenoic fatty acids to produce proinflammatory lipids. 12/15-LO is expressed in macrophages and pancreatic ␤-cells. It enhances interleukin 12 production by macrophages, and several of its products induce apoptosis of ␤-cells at nanomolar concentrations in vitro. We had previously demonstrated a role for 12/15-LO in ␤-cell damage in the streptozotocin model of diabetes. Since the gene encoding 12/15-LO (gene designation Alox15) lies within the Idd4 diabetes susceptibility interval in NOD mice, we hypothesized that 12/15-LO is also a key regulator of diabetes susceptibility in the NOD mouse. RESEARCH DESIGN AND METHODS-We developed NOD mice carrying an inactivated 12/15-LO locus (NOD-Alox15null ) using a "speed congenic" protocol, and the mice were monitored for development of insulitis and diabetes.RESULTS-NOD mice deficient in 12/15-LO develop diabetes at a markedly reduced rate compared with NOD mice (2.5 vs. Ͼ60% in females by 30 weeks). Nondiabetic female NOD-Alox15 null mice demonstrate improved glucose tolerance, as well as significantly reduced severity of insulitis and improved ␤-cell mass, when compared with age-matched nondiabetic NOD females. Disease resistance is associated with decreased numbers of islet-infiltrating activated macrophages at 4 weeks of age in NOD-Alox15 null mice, preceding the development of insulitis. Subsequently, islet-associated infiltrates are characterized by decreased numbers of CD4 ϩ T cells and increased Foxp3 ϩ cells.CONCLUSIONS-These results suggest an important role for 12/15-LO in conferring susceptibility to autoimmune diabetes in NOD mice through its effects on macrophage recruitment or activation.

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Section: Discussionmentioning

confidence: 49%

Nonobese Diabetic (NOD) Mice Congenic for a Targeted Deletion of 12/15-Lipoxygenase Are Protected From Autoimmune Diabetes

et al. 2008

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“…EGT is a common procedure for efficient targeted transduction of genes of interest. It has been applied to numerous tissues and organs in several animal models [13][14][15][16][17][18] and, in particular, it has been proposed to improve transfection of skeletal muscle with plasmid DNA [16,[19][20][21][22][23][24][25]. EGT has significantly improved muscle gene transduction, allowing a several fold increase in the amount of recombinant protein produced.…”

Section: Discussionmentioning

confidence: 99%

“…Electro gene transfer (EGT) is a highly efficient method of delivering exogenous molecules into cells. It has been used to introduce DNA into various mouse and rat tissues [13][14][15][16][17][18] and it has also been successfully proposed to improve transfection of skeletal muscle with plasmid DNA [16,[19][20][21][22][23][24][25]. In fact, although muscle represents a very accessible tissue, and therefore a good gene transfer target, many drawbacks in obtaining high transfection efficiencies had been previously described by using direct injection [26,27].…”

Section: Accepted Manuscript Introductionmentioning

confidence: 99%

Gene therapy of Hunter syndrome: Evaluation of the efficiency of muscle electro gene transfer for the production and release of recombinant iduronate-2-sulfatase (IDS)

Friso

Tomanin²,

Zanetti³

et al. 2008

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Mucopolysaccharidosis type II (MPSII) is an inherited disorder due to a deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS). The disease is characterized by a considerable deposition of heparan- and dermatan-sulfate, causing a general impairment of physiological functions. Most of the therapeutic protocols proposed so far are mainly based upon enzyme replacement therapy which is very expensive. There is a requirement for an alternative approach, and to this aim, we evaluated the feasibility of muscle electro gene transfer (EGT) performed in the IDS-knockout (IDS-ko) mouse model. EGT is a highly efficient method of delivering exogenous molecules into different tissues. More recently, pre-treatment with bovine hyaluronidase has shown to further improve transfection efficiency of muscle EGT. We here show that, by applying such procedure, IDS was very efficiently produced inside the muscle. However, no induced IDS activity was measured in the IDS-ko mice plasma, in contrast to matched healthy controls. In the same samples, an anticipated and rapidly increasing immune response against the recombinant protein was observed in the IDS-ko vs control mice, although reaching the same levels at 5 weeks post-injection. Additional experiments performed on healthy mice showed a significant contribution of hyaluronidase pre-treatment in increasing the immune response.

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“…transfer and that i.s. electro-gene transfer may represent a new approach to cytokine therapy in autoimmune diseases [20].…”

Section: Interleukin-4mentioning

confidence: 99%

Gene therapy of multiple sclerosis

Furlan¹,

Maiorino²,

Gatta³

et al. 2010

Gene Therapy for Autoimmune and Inflammatory Diseases

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Multiple sclerosis (MS) constitutes a difficult challenge for the design of innovative therapies: the aetiology is unknown, the pathogenesis only partially understood, and the whole process is multi-focal, chronic, and occurring beyond anatomical barriers, making the delivery of potentially therapeutic molecules difficult. Gene therapy, thus, constitutes a realistic alternative to ensure prolonged, and site-specific delivery of therapies. Recent advancements in the comprehension of the immunopathological processes leading to central nervous system inflammation, and the development of new gene therapy tools, such as RNA-interference, are rapidly leading to a large array of possibilities of intervention, documented in the present review in its animal model, experimental autoimmune encephalomyelitis (EAE). Since progressive forms of MS remain orphan of efficient therapies, the field is open for less conventional interventions such as gene therapy.

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Intrasplenic electro-transfer of IL-4 encoding plasmid DNA efficiently inhibits rat experimental allergic encephalomyelitis

Cited by 11 publications

References 35 publications

Nonobese Diabetic (NOD) Mice Congenic for a Targeted Deletion of 12/15-Lipoxygenase Are Protected From Autoimmune Diabetes

Nonobese Diabetic (NOD) Mice Congenic for a Targeted Deletion of 12/15-Lipoxygenase Are Protected From Autoimmune Diabetes

Gene therapy of Hunter syndrome: Evaluation of the efficiency of muscle electro gene transfer for the production and release of recombinant iduronate-2-sulfatase (IDS)

Gene therapy of multiple sclerosis

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