Protection against collagen-induced arthritis by electrotransfer of an expression plasmid for the interleukin-4

Ho, Seong-Hyun; Hahn, Woong; Lee, Hwang-Jae; Kim, Joo Young; Jeong, Jae-Gyun; Kim, Sujeong; Yu, Seung Shin; Jeon, Eun‐Seok; Kim, Sun‐Young; Kim, Jong-Mook

doi:10.1016/j.bbrc.2004.07.028

Cited by 32 publications

(11 citation statements)

References 39 publications

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“…Th2 cells secrete cytokines, including IL-4, IL-6, and IL-10. IL-4 stimulates the proliferation of T cells and B cells and studies [26] have shown that IL-4 stimulates human mononuclear cells to produce IL-1 receptor antagonist (IL-1Ra), which, in turn, inhibit the colony formation and migration of macrophages. IL-4 therefore plays a crucial role in controlling inflammation.…”

Section: Discussionmentioning

confidence: 99%

Exogenous IL-4-Expressing Bone Marrow Mesenchymal Stem Cells for the Treatment of Autoimmune Sensorineural Hearing Loss in a Guinea Pig Model

Tan

Gao

Guo

et al. 2014

BioMed Research International

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Bone marrow mesenchymal stem cells (BMSCs) expressing recombinant IL-4 have the potential to remediate inflammatory diseases. We thus investigated whether BMSCs expressing exogenous IL-4 could alleviate autoimmune sensorineural hearing loss. BMSCs isolated from guinea pigs were transfected with recombinant lentivirus expressing IL-4. A total of 33 animals were divided into three groups. Group A received scala tympani injection of IL-4-expressing BMSCs, and Group B received control vector-expressing BMSCs, and Group C received phosphate-buffered saline. The distribution of implanted BMSCs in the inner ears was assessed by immunohistochemistry and fluorescence microscopy. Auditory brain-stem response (ABR) was monitored to evaluate the auditory changes. Following BMSCs transplantation, the threshold levels of ABR wave III decreased in Groups A and B and significant differences were observed between these two groups (P < 0.05). Transplanted BMSCs distributed in the scala tympani and scala vestibuli. In some ears with hearing loss, there was a decrease in the number of spiral ganglion cells and varying degrees of endolymphatic hydrops or floccule. Following transplantation, the lentivirus-infected BMSCs migrated to the inner ear and produced IL-4. Our results demonstrate that, upon transplantation, BMSCs and BMSCs expressing recombinant IL-4 have the ability to remediate the inflammatory injury in autoimmune inner ear diseases.

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Section: Discussionmentioning

confidence: 99%

Exogenous IL-4-Expressing Bone Marrow Mesenchymal Stem Cells for the Treatment of Autoimmune Sensorineural Hearing Loss in a Guinea Pig Model

Tan

Gao

Guo

et al. 2014

BioMed Research International

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“…In the right panels, quantification of bands by densitometry from two experiments is depicted. Lubberts et al, 1999;Ho et al, 2004]. The observed inhibition of proinflammatory cytokine-stimulated bovine cartilage explant degradation by IL-4 [Yeh et al, 1995;Cawston et al, 1996;Salter et al, 1996] may be due to its ability to completely or partially inhibit MMP-13 and ADAMTS-4 demonstrated here.…”

Section: Discussionmentioning

confidence: 41%

Interleukin‐4 antagonizes oncostatin M and transforming growth factor beta‐induced responses in articular chondrocytes

Mabrouk

Qureshi

et al. 2007

J of Cellular Biochemistry

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Oncostatin M (OSM) stimulates cartilage degradation in rheumatoid arthritis (RA) by inducing matrix metalloproteinases (MMPs) and aggrecanases (ADAMTS; a disintegrin and metalloproteinase with thrombospondin motif). Transforming growth factor beta (TGF-beta1) induces cartilage repair in joints but in excessive amounts, promotes inflammation. OSM and TGF-beta1 also induce tissue inhibitor of metalloproteinase-3 (TIMP-3), an important natural inhibitor of MMPs, aggrecanases, and tumor necrosis factor alpha converting enzyme (TACE), the principal proteases involved in arthritic inflammation and cartilage degradation. We studied cartilage protective mechanisms of the antiinflammatory cytokine, interleukin-4 (IL-4). IL-4 strongly (MMP-13 and TIMP-3) or minimally (ADAMTS-4) suppressed OSM-induced gene expression in chondrocytes. IL-4 did not affect OSM-stimulated phosphorylation of extracellular signal-regulated kinases (ERKs), protein 38 (p38), c-Jun N-terminal kinase (JNK) and Stat1. Lack of additional suppression with their inhibitors suggested that MMP-13, ADAMTS-4, and TIMP-3 inhibition was independent of these mediators. IL-4 also downregulated TGF-beta1-induced TIMP-3 gene expression, Smad2, and JNK phosphorylation. Additional suppression of TIMP-3 RNA by JNK inhibitor suggests JNK implication. The cartilage protective effects of IL-4 in animal models of arthritis may be due to its inhibition of MMPs and ADAMTS-4 expression. However, suppression of TIMP-3 suggests caution for using IL-4 as a cartilage protective therapy.

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“…In a variety of studies of in vivo gene electrotransfer it was shown that different electric pulse parameters can be used for efficient transfection [32]: 1) relatively short pulses of 6 × 100 μs [86]; 2) relatively long and low pulses, e.g. 8 × 20 ms [35,80,87-89]; and 3) combination of high-voltage and low-voltage pulses [47,71,90-93]. To use the presented numerical optimization for different pulses, the electroporation thresholds would have to be determined and built into the electroporation models.…”

Section: Discussionmentioning

confidence: 99%

Numerical optimization of gene electrotransfer into muscle tissue

et al. 2010

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BackgroundElectroporation-based gene therapy and DNA vaccination are promising medical applications that depend on transfer of pDNA into target tissues with use of electric pulses. Gene electrotransfer efficiency depends on electrode configuration and electric pulse parameters, which determine the electric field distribution. Numerical modeling represents a fast and convenient method for optimization of gene electrotransfer parameters. We used numerical modeling, parameterization and numerical optimization to determine the optimum parameters for gene electrotransfer in muscle tissue.MethodsWe built a 3D geometry of muscle tissue with two or six needle electrodes (two rows of three needle electrodes) inserted. We performed a parametric study and optimization based on a genetic algorithm to analyze the effects of distances between the electrodes, depth of insertion, orientation of electrodes with respect to muscle fibers and applied voltage on the electric field distribution. The quality of solutions were evaluated in terms of volumes of reversibly (desired) and irreversibly (undesired) electroporated muscle tissue and total electric current through the tissue.ResultsLarge volumes of reversibly electroporated muscle with relatively little damage can be achieved by using large distances between electrodes and large electrode insertion depths. Orienting the electrodes perpendicular to muscle fibers is significantly better than the parallel orientation for six needle electrodes, while for two electrodes the effect of orientation is not so pronounced. For each set of geometrical parameters, the window of optimal voltages is quite narrow, with lower voltages resulting in low volumes of reversibly electroporated tissue and higher voltages in high volumes of irreversibly electroporated tissue. Furthermore, we determined which applied voltages are needed to achieve the optimal field distribution for different distances between electrodes.ConclusionThe presented numerical study of gene electrotransfer is the first that demonstrates optimization of parameters for gene electrotransfer on tissue level. Our method of modeling and optimization is generic and can be applied to different electrode configurations, pulsing protocols and different tissues. Such numerical models, together with knowledge of tissue properties can provide useful guidelines for researchers and physicians in selecting optimal parameters for in vivo gene electrotransfer, thus reducing the number of animals used in studies of gene therapy and DNA vaccination.

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Protection against collagen-induced arthritis by electrotransfer of an expression plasmid for the interleukin-4

Cited by 32 publications

References 39 publications

Exogenous IL-4-Expressing Bone Marrow Mesenchymal Stem Cells for the Treatment of Autoimmune Sensorineural Hearing Loss in a Guinea Pig Model

Exogenous IL-4-Expressing Bone Marrow Mesenchymal Stem Cells for the Treatment of Autoimmune Sensorineural Hearing Loss in a Guinea Pig Model

Interleukin‐4 antagonizes oncostatin M and transforming growth factor beta‐induced responses in articular chondrocytes

Numerical optimization of gene electrotransfer into muscle tissue

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