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ABSTRACT: Adsorption behaviors of recombinant E-cadherin-IgG Fc (E-cad-Fc) fusion protein and mutated E-cad-Fcs on the polystyrene (PS) surface were investigated using a 27 MHz quartz-crystal microbalance (QCM) and ELISA. The amount of adsorbed E-cad-Fc on PS surface was increased with an increase of E-cad-Fc concentration as a Langmuir-type in a monolayer. Adsorbed E-cad-Fc on PS surface was stable even after washing if calcium ions are absent in the washing solution due to the calcium ion dependence in the adsorption. E-cadherin homophilic adhesion among E-cadherins during adsorption of E-cad-Fc was involved. Deglycosylation of the E-cad in the E-cad-Fc did not affect adsorption of E-cad-Fc on the PS surface although deglycosylation of the E-cad in the E-cad-Fc enhanced cell adhesion compared with E-cad-Fc.
Colloids and surfaces. B, Biointerfaces 02/2012; 94:192-8. · 2.60 Impact Factor
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ABSTRACT: We investigated the causes of death and analyzed the prognostic factors in Korean systemic lupus erythematosus (SLE) patients. We evaluated 1010 patients with SLE who visited Seoul Saint Mary's Hospital from 1997-2007. Changing patterns in the causes of death were analyzed. Survival rate was calculated by the Kaplan-Meier method and the log-rank test. The risk factors for death were analyzed by multivariate logistic regression analysis. The 5-year survival rate was 97.8%. Over the period of the study, 59 deaths were observed. Among 44 patients who died in our hospital, the most common cause of death was infection (37.3%), with SLE-related death as the next most frequent cause (22.0%). In comparison with earlier data, the proportion of SLE-related deaths has fallen and the proportion of infections has risen. SLE-related death was the most frequent cause of early death, while infection was the most common cause of death in the overall population. In univariate analysis, damage related to SLE, cumulative glucocorticoid dose, mean glucocorticoid dose for 1 month before death, intravenous methylprednisolone therapy and cyclophosphamide treatment were associated with death (p < 0.001 each). The late onset of SLE and renal involvement were predictive factors of poor outcome (p = 0.03 and p < 0.001). In multivariate analysis, the risk factors for death were irreversible damage related to SLE, cyclophosphamide therapy and mean glucocorticoid dose for 1 month before death. The most common cause of death in Korean SLE patients was infection. The judicious use of immunosuppressive agents may be important to decrease infection and to improve survival in SLE patients.
Lupus 06/2011; 20(9):989-97. · 2.34 Impact Factor
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ABSTRACT: Meningitis is a rare complication of systemic lupus erythematosus (SLE), potentially leading to a fatal outcome. The demographic, clinical, and laboratory features, and the outcomes of meningitis were evaluated in Korean patients with SLE. In a retrospective medical record review of 1420 SLE patients, 20 patients who had developed septic or aseptic meningitis were identified. In 11 patients, the causative microorganisms were identified ('septic meningitis'), and Cryptococcus neoformans was the major pathogen. The other nine patients were diagnosed with aseptic meningitis. The patients with septic meningitis were older than those with aseptic meningitis (p = 0.025) and displayed mental changes more often (p = 0.005). Leukocyte counts in the cerebrospinal fluid (CSF) were higher (p = 0.044) and the levels of CSF glucose were lower in the septic meningitis group (p = 0.036). Plasma leukocyte counts and neutrophil counts were higher in patients with septic meningitis (p = 0.037 and p = 0.020, respectively). Meningitis was observed in 1.4% of Korean patients with SLE and, in 55% of the meningitis patients, microorganisms were isolated and Cryptococcus neoformans was most commonly identified. Altered mental status, plasma leukocytosis, neutrophilia, and CSF pleocytosis and hypoglycemia were more prominent in patients with septic meningitis.
Lupus 01/2011; 20(5):531-6. · 2.34 Impact Factor
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ABSTRACT: Cancer gene therapy using tumor suppressor genes is considered to be an attractive approach for arresting cell growth and inducing apoptosis. Programmed cell death 4 (Pdcd4) is a tumor suppressor gene, which prevents tumorigenesis and tumor progression. To address the issue of whether expression of PDCD4 protein induces apoptosis in cancerous cells, the Pdcd4 gene was delivered using folate-PEG-baculovirus. Folate-PEG-baculovirus containing Pdcd4 gene (F-P-Bac-Pdcd4) was constructed by attachment of F-PEG to the baculovirus surface using chemical modification. The F-P-Bac-Pdcd4 showed enhanced transduction efficiency, efficiently expressed PDCD4 protein, and induced apoptosis in human epidermal carcinoma (KB) cells as compared with an unmodified baculovirus. In a tumor xenograft study, injection of F-P-Bac-Pdcd4 into tumors established from the KB cell line by subcutaneous implantation significantly suppressed tumor growth and induced apoptosis. Thus, this study shows a new baculovirus-mediated tumor suppressor gene delivery system for cancer therapy.
Cancer gene therapy 11/2010; 17(11):751-60. · 3.13 Impact Factor
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ABSTRACT: This study was undertaken to investigate clinical characteristics of diffuse alveolar hemorrhage (DAH) in patients with systemic lupus erythematosus (SLE) and to determine risk factors and clinical outcomes of DAH in SLE patients. Among the 1521 patients with SLE admitted between January 1993 and June 2009 to affiliated hospitals of Catholic University of Korea, 21 SLE were admitted for DAH. The inclusion criteria for DAH was defined as new infiltrates on chest radiographs, an acute hemoglobin drop of at least 1.5 g/dl in the absence of an obvious source of bleeding, and one or more of the following signs: hemoptysis, hypoxemia, bronchoscopic or biopsy evidence of DAH. Included as disease controls were 83 SLE patients, matched for age and sex, who were admitted for other manifestations. Data based on medical records were analyzed retrospectively. There were no significantly differing demographic characteristics between SLE patients with DAH and those with other manifestations. Multivariate analysis demonstrated coexisting neuropsychiatric lupus (p = 0.002) and high SLE disease activity index scores (SLEDAI > 10) as independent risk factors in the development of DAH (p = 0.029). Among the 21 SLE patients with DAH, 13 died during the admission period (in-hospital mortality rate: 61.9%). Mortality was associated with infection and requirements of mechanical ventilation. Collectively, SLE patients who have neuropsychiatric manifestations or are in the active stage of the disease have an increased risk for developing DAH. Due to the high mortality of SLE patients with DAH, early recognition of risk factors and appropriate intervention is essential.
Lupus 10/2010; 20(1):102-7. · 2.34 Impact Factor
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ABSTRACT: Defective control of T cell apoptosis is considered to be one of the pathogenetic mechanisms in systemic lupus erythematosus (SLE). Oestrogen has been known to predispose women to SLE and also to exacerbate activity of SLE; however, the role of oestrogen in the apoptosis of SLE T cells has not yet been documented. In this study, we investigated the direct effect of oestrogen on the activation-induced cell death of T cells in SLE patients. The results demonstrated that oestradiol decreased the apoptosis of SLE T cells stimulated with phorbol 12-myristate 13-acetate (PMA) plus ionomycin in a dose-dependent manner. In addition, oestradiol down-regulated the expression of Fas ligand (FasL) in activated SLE T cells at the both protein and mRNA levels. In contrast, testosterone increased FasL expression dose-dependently in SLE T cells stimulated with PMA plus ionomycin. The inhibitory effect of oestradiol on FasL expression was mediated through binding to its receptor, as co-treatment of tamoxifen, an oestrogen receptor inhibitor, completely nullified the oestradiol-induced decrease in FasL mRNA expression. Moreover, pre-treatment of FasL-transfected L5178Y cells with either oestradiol or anti-FasL antibody inhibited significantly the apoptosis of Fas-sensitive Hela cells when two types of cells were co-cultured. These data suggest that oestrogen inhibits activation-induced apoptosis of SLE T cells by down-regulating the expression of FasL. Oestrogen inhibition of T cell apoptosis may allow for the persistence of autoreactive T cells, thereby exhibiting the detrimental action of oestrogen on SLE activity.
Clinical & Experimental Immunology 09/2010; 161(3):453-8. · 3.36 Impact Factor
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ABSTRACT: Gene therapy continues to hold promise in treating a variety of inherited and acquired diseases. The great majority of gene therapy trials rely on viral vectors for gene transduction because of their high efficiency. Non-viral vectors for gene delivery are receiving increasing attention for application in a wide variety of gene mediated therapies for humans. Polycationic polymers have been increasingly proposed as potential vectors because of their versatility. Rigidity, hydrophobicity/hydrophilicity, charge density, biodegradability, and molecular weight of the polymer chain are all parameters that in principle can be adjusted to achieve an optimal complexation with DNA. Polymers with repeating polyester bonds in the backbone are structurally versatile and biodegradable through hydrolysis, and possibly enzymatic digestion at the ester linkages under physiological conditions. These biodegradable polyesters are appealing for biological and pharmaceutical applications because of their potential biocompatibility and similarity to bio-macromolecules such as nucleic acids. In this review, we focuses on characteristics of polyesters as gene delivery carrier, degradation pattern as an essential parameter for reduced toxicity, classification based on its physicochemical properties followed by its success as efficient gene delivery carrier in vitro and in vivo. We will also discuss the conjugation of ligands/charged groups to the side chain of the polyester, constituting target specific moieties such as folate in order to achieve receptor mediated endocytosis as well as target specific delivery of DNA. Capable of delivering exogenous genes to a cell nucleus, these cationic polyesters also serve as a valuable model to understand the important characteristics that render a polymer an effective gene carrier.
Materials Technology 08/2010; 25(3-4):196-204. · 0.59 Impact Factor
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ABSTRACT: Mesenchymal stem cells (MSCs) have the inherent ability to migrate to multiple organs and to exert immunosuppressive activity. The aim of this study was to investigate the anti-arthritogenic effects of interleukin (IL)-10-transduced MSCs (IL-10-MSC) on the development of inflammatory arthritis. DBA/1 mice were immunized with type II collagen (CII) to induce inflammatory arthritis and then injected weekly three times with IL-10-MSCs 21 days after primary immunization. Control mice received vehicle or MSCs alone. Serum anti-CII antibody and T cell response to CII were determined. The results showed that cultured IL-10-MSCs were able to secrete high amounts of IL-10 in vitro. Injection of IL-10-MSCs decreased the severity of arthritis significantly. However, there was no difference in arthritis severity between mice treated with MSC and vehicle alone. Anti-CII antibody titres in the sera and T cell proliferative response to CII in lymph node cells were decreased significantly in mice treated with IL-10-MSCs compared with vehicle-treated mice. Serum IL-6 level was also decreased by the administration of IL-10-MSCs. In contrast, spleen cells of IL-10-MSC-treated mice produced higher amounts of IL-4 than those of control mice. Interestingly, although not as potent as IL-10-MSCs, injection of naive MSCs alone decreased serum levels of IL-6 and anti-CII antibody, while increasing IL-4 production from cultured splenic cells. Taken together, systemic administration of genetically modified MSCs overexpressing IL-10 inhibits experimental arthritis not only by suppressing autoimmune response to CII but also by regulating cytokine production, and thus would be a new strategy for treating rheumatoid arthritis.
Clinical & Experimental Immunology 09/2008; 153(2):269-76. · 3.36 Impact Factor
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ABSTRACT: Gene therapy is a powerful treatment for inborn and acquired diseases. The development of safe and effective gene delivery systems is a great challenge to make the human gene therapy a reality. Viral vectors have been commonly employed due to the high transfection efficiency, however, their application to the human body is often frustrated by immunogenicity, potential infectivity, complicated production, and inflammation. Non-viral vectors have been widely proposed as safer alternatives to viral vectors by reason of unique advantages such as less immune reaction against repeated administration, ease of synthesis, cell/tissue targeting, unrestricted plasmid size, and low cost. Among non-viral systems, cationic polymers have gained increasing attention because they can easily form self-assembly with DNA. Polyethylenimine (PEI) is one of the most popular cationic polymers investigated in non-viral gene therapy due to its ability to generate elevated levels of gene expression in vitro and in vivo compared to another non-viral carriers. However, the PEI showed high cytotoxicity, which depends on the molecular weight of the PEI. Recently, the degradable PEIs were synthesised to have high transfection efficiency with low cytotoxicity. The present review describes recent progress on the development of degradable PEIs as non-viral vectors. The present paper also summarises structure of degradable PEIs–transfection relationship to provide a novel insight with respect to this type of gene delivery system. First, linear degradable polymers based on linear PEIs are represented. Second, branched polymers based on branched PEIs are discussed. Third, grafted degradable copolymers based on branched PEIs are explained.
Materials Science and Technology 08/2008; 24(9):1118-1126. · 0.77 Impact Factor
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H Jin,
C-X Xu,
H-W Kim,
Y-S Chung,
J-Y Shin,
S-H Chang,
S-J Park,
E-S Lee,
S-K Hwang,
J-T Kwon,
A Minai-Tehrani,
M Woo,
M-S Noh,
H-J Youn,
D-Y Kim,
B-I Yoon,
K-H Lee,
T-H Kim, C-S Cho,
M-H Cho
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ABSTRACT: The low efficiency of conventional therapies in achieving long-term survival of lung cancer patients calls for development of novel options. Revisiting of aerosol gene delivery may provide an alternative for safe and effective treatment for lung cancer. In this study, imidazole ring-containing urocanic acid-modified chitosan (UAC) designed in the previous study was used as a gene carrier. The potential effects of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) on Akt-related signals and cell cycle regulation were evaluated. Aerosols of UAC-PTEN were delivered into K-ras(LA1) lung cancer model mice through the nose-only inhalation system twice a week for total 4 weeks. Delivered PTEN suppressed lung tumor development significantly through nuclear complex formation between PTEN and p53, suppressing Akt-related signals as well as cell cycle regulation. Together, our results suggest that aerosol delivery of UAC-PTEN may be compatible with noninvasive in vivo gene therapy.
Cancer gene therapy 06/2008; 15(5):275-83. · 3.13 Impact Factor
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ABSTRACT: Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that has been demonstrated to regulate the apoptosis of several cell types. Dysregulated apoptosis of fibroblasts has been implicated in a variety of fibrotic diseases, including systemic sclerosis (SSc). In this study, we investigated the role of MIF in the apoptosis of dermal fibroblasts. The concentrations of MIF were measured in sera and in culture supernatants of peripheral blood mononuclear cells (PBMCs) and dermal fibroblasts by enzyme-linked immunosorbent assay. The degree of apoptosis was determined by colorimetric assay, and signalling pathways were examined by Western blot. The results showed that serum levels of MIF were significantly higher in patients with SSc (n = 47) than in healthy controls (n = 56). Stimulation of PBMCs by anti-CD3 and anti-CD28 increased the production of MIF by fourfold over the constitutive levels. SSc dermal fibroblasts produced higher amounts of MIF than normal dermal fibroblasts. When treated with sodium nitroprusside (SNP), SSc dermal fibroblasts showed a lower degree of apoptosis compared with normal dermal fibroblasts. Exogenous MIF (1-100 ng/ml) inhibited SNP-induced apoptosis of dermal fibroblasts dose-dependently. Both extracellular regulated kinase (ERK) inhibitor (PD98059) and protein kinase B (Akt) inhibitor (LY294002) almost completely blocked the inhibitory effect of MIF on apoptosis. Furthermore, MIF increased the expression of Bcl-2, phospho-ERK and phospho-Akt activity in dermal fibroblasts. Taken together, our data suggest that MIF released by activated T cells and dermal fibroblasts decreases the apoptosis of dermal fibroblasts through activation of ERK, Akt and Bcl-2 signalling pathways, which might be associated with excessive fibrosis in SSc.
Clinical & Experimental Immunology 06/2008; 152(2):328-35. · 3.36 Impact Factor
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H-L Jiang,
J-T Kwon,
Y-K Kim,
E-M Kim,
R Arote,
H-J Jeong,
J-W Nah,
Y-J Choi,
T Akaike,
M-H Cho, C-S Cho
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ABSTRACT: Chitosans have been proposed as alternative, biocompatible cationic polymers for nonviral gene delivery. However, the low transfection efficiency and low specificity of chitosan need to be addressed before clinical application. We prepared galactosylated chitosan-graft-polyethylenimine (GC-g-PEI) copolymer by an imine reaction between periodate-oxidized GC and low-molecular-weight PEI. The molecular weight and composition were characterized using gel permeation chromatography column with multi-angle laser scattering and (1)H nuclear magnetic resonance, respectively. The copolymer was complexed with plasmid DNA in various copolymer/DNA (N/P) charge ratios, and the complexes were characterized. GC-g-PEI showed good DNA-binding ability and superior protection of DNA from nuclease attack and had low cytotoxicity compared to PEI 25K. GC-g-PEI/DNA complexes showed higher transfection efficiency than PEI 25K in both HepG2 and HeLa cell lines. Transfection efficiency into HepG2, which has asialoglycoprotein receptors, was higher than that into HeLa, which does not. GC-g-PEI/DNA complexes also transfected liver cells in vivo after intraperitoneal (i.p.) administration more effectively than PEI 25K. These results suggest that GC-g-PEI can be used in gene therapy to improve transfection efficiency and hepatocyte specificity in vitro and in vivo.
Gene Therapy 11/2007; 14(19):1389-98. · 3.71 Impact Factor
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ABSTRACT: Chitosan has been investigated as a non-viral vector because it has several advantages such as biocompatibility, biodegradability and low toxicity with high cationic potential. However, the low specificity and low transfection efficiency of chitosan need to be solved prior to clinical application. In this paper, we focused on the galactose or mannose ligand modification of chitosan for enhancement of cell specificity and transfection efficiency via receptor-mediated endocytosis in vitro and in vivo.
Biomedical Materials 10/2007; 2(3):S95-100. · 2.16 Impact Factor
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S-K Hwang,
H Jin,
J T Kwon,
S-H Chang,
T H Kim, C-S Cho,
K H Lee,
M R Young,
N H Colburn,
G R Beck,
H-S Yang,
M-H Cho
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ABSTRACT: The long-term survival of lung cancer patients treated with conventional therapies remains poor and therefore the need for novel approaches remains high. This has led to the re-emergence of aerosol delivery as a therapeutic intervention. In this study, glucosylated polyethylenimine (GPEI) was used as carrier to investigate programmed cell death 4 (PDCD4) and PDCD4 mutant (D418A), an eIF4A-binding mutant, on PDCD4-related signaling and activator protein-1 (AP-1) activity in the lungs of AP-1 luciferase reporter mice. After confirming the efficiency of GPEI as a carrier in lungs, the effects of aerosol-delivered PDCD4 were investigated in AP-1 luciferase reporter mice. Aerosol delivery of GPEI/PDCD4 through a nose-only inhalation facilitated the apoptosis of lungs whereas aerosol PDCD4 mutant did not. Also, such aerosol delivery regulated proteins relevant to cell-cycle control and suppressed AP-1 activity. Results obtained by western blot analysis, immunohistochemistry, luciferase assay and deoxynucleotidyl-transferase-mediated nick end labeling study suggest that combined actions such as facilitating apoptosis, controlling cell cycle and suppression of AP-1 activity by PDCD4 may provide useful tool for designing lung tumor prevention and treatment by which PDCD4 functions as a transformation suppressor in the future.
Gene Therapy 10/2007; 14(18):1353-61. · 3.71 Impact Factor
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ABSTRACT: We have elsewhere reported the work on the preparation of semi-interpenetrating polymer networks (SIPNs) composed of chitosan (CS) and poloxamer to improve the mechanical strength of CS sponge. This study focuses on evaluation of the CS/poloxamer SIPNs to intend for wound dressing application and the efficacy of dehydroepiandrosterone (DHEA)-loaded CS/poloxamer SIPNs in the wound model studies. The properties required for ideal wound dressing, such as equilibrium water content (EWC), water absorption (A(w)), water vapor transmission rate (WVTR), and evaporative water loss, were examined. The CS/poloxamer SIPNs were found to have a water content of 90% of their weight which could prevent the wound bed from accumulation of exudates and also have excellent water adsorption. The WVTR of CS/poloxamer SIPNs was found to be 2,508.2+/-65.7gm(-2)day(-1), indicating that the SIPNs can maintain a moist environment over wound bed in moderate to heavily exuding wound which enhances epithelial cell migration during the healing process. Also, the CS/poloxamer SIPNs in vitro assessment showed proper biodegradation and low cytotoxicity for wound dressing application. The wound healing efficacy of CS/poloxamer SIPNs as a wound dressing was evaluated on experimental full thickness wounds in a mouse model. It was found that the wounds covered with CS/poloxamer SIPNs or DHEA-loaded CS/poloxamer SIPNs were completely filled with new epithelium without any significant adverse reactions after 3 weeks. The results thus indicate that CS/poloxamer SIPNs could be employed in the future as potential wound dressing materials.
International Journal of Pharmaceutics 09/2007; 341(1-2):35-43. · 3.35 Impact Factor
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H S Moon,
D D Guo,
H H Song,
I Y Kim,
H L Jiang,
H L Jin,
Y K Kim,
C S Chung,
Y J Choi,
H K Lee, C S Cho
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ABSTRACT: Obesity is major risk factor for many disorders, including diabetes, hypertension and heart disease. Unfortunately, there is a dearth of therapeutic agents available to clinicians for the treatment of obesity. The principal aim of this study was to investigate whether PEGylated all-trans retinoic acid (PRA) can have favorable stability and biological activity in 3T3-L1 preadipocytes as an antiobesity drug. Here, we found that PRA inhibits the process of adipogenesis, including survival of adipocytes and differentiation to mature adipocytes. The results showed that RA nanoparticles (NPs) were prepared by PEGylation; below 200 nm, PRA-NPs were obtained. Moreover, PRA decreased glycerol-3-phosphate dehydrogenase activity in 3T3-L1 preadipocytes by acting with major adipocyte marker proteins such as PPARgamma2, C/EBPalpha and aP2 modulators. Apoptosis, in addition, increased as the level of RA increased from 10 to 20 microM, whereas PRA reduced apoptosis with increasing concentrations. Our data suggest that PRA-NP has potential as an antiobesity drug carrier due to its small particle size and PEGylated core-shell structure. In addition, our results suggest that PRA inhibits the process of adipogenesis and may be developed to treat obesity. Based on these results, PRA is suitable for adipocyte studies, and an enhanced effect of PRA with adipocyte differentiation offers a challenging approach for pharmaceutical applications.
The Journal of Nutritional Biochemistry 06/2007; 18(5):322-31. · 3.89 Impact Factor
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ABSTRACT: Interleukin (IL)-4 has been demonstrated to have anti-inflammatory and anti-tumour activity. Because aberrant angiogenesis is a significant pathogenic component of tumour growth and chronic inflammation, we investigated the effect of IL-4 on the production of vascular endothelial growth factor (VEGF) by synovial fibroblasts derived from patients with rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLS) were prepared from synovial tissues of RA and incubated with different concentrations of IL-4 in the presence or absence of transforming growth factor (TGF)-beta. VEGF level was measured by enzyme-linked immunosorbent assay and semiquantitative reverse transcription--polymerase chain reaction. Treatment of FLS with IL-4 alone caused a dose-dependent increase in VEGF levels. In contrast, IL-4 exhibited the inhibitory effect on VEGF production when FLS were stimulated with TGF-beta. Combined treatment of IL-4 and IL-10 inhibited TGF-beta-induced VEGF production in an additive fashion. TGF-beta increased the induction of cyclooxygenase-2 mRNA, which was inhibited significantly by the treatment of IL-4. NS-398, a COX-2 inhibitor, inhibited TGF-beta-induced VEGF production in a dose-dependent manner. Furthermore, exogenous addition of prostaglandin E2 (PGE2) restored IL-4 inhibition on TGF-beta induced VEGF production. Collectively, our results suggest that IL-4 have an anti-angiogenic effect, especially in the inflammatory milieu of RA by inhibiting the VEGF production in synovial fibroblasts.
Clinical & Experimental Immunology 04/2007; 147(3):573-9. · 3.36 Impact Factor
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A M Tehrani,
S-K Hwang,
T-H Kim, C-S Cho,
J Hua,
W-S Nah,
J-T Kwon,
J-S Kim,
S-H Chang,
K-N Yu,
S-J Park,
D R Bhandari,
K-H Lee,
G-H An,
G R Beck,
M-H Cho
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ABSTRACT: Lung cancer has emerged as a leading cause of cancer death in the world; however, most of the current conventional therapies are not sufficiently effective in altering the progression of disease. Therefore, development of novel treatment approaches is needed. Although several genes and methods have been used for cancer gene therapy, a number of problems such as specificity, efficacy and toxicity reduce their application. This has led to re-emergence of aerosol gene delivery as a noninvasive method for lung cancer treatment. In this study, nano-sized glucosylated polyethyleneimine (GPEI) was used as a gene delivery carrier to investigate the effects of Akt wild type (WT) and kinase deficient (KD) on Akt-related signaling pathways and protein translation in the lungs of CMV- LucR-cMyc-IRES-LucF dual reporter mice. These mice are a powerful tool for the discrimination between cap-dependent/-independent protein translation. Aerosols containing self-assembled nano-sized GPEI/Akt WT or GPEI/Akt KD were delivered into the lungs of reporter mice through nose-only-inhalation-chamber with the aid of nebulizer. Aerosol delivery of Akt WT caused the increase of protein expression levels of Akt-related signals, whereas aerosol delivery of Akt KD did not. Furthermore, dual luciferase activity assay showed that aerosol delivery of Akt WT enhanced cap-dependent protein translation, whereas a reduction in cap-dependent protein translation by Akt KD was observed. Our results clearly showed that targeting Akt may be a good strategy for prevention as well as treatment of lung cancer. These studies suggest that our aerosol delivery is compatible for in vivo gene delivery which could be used as a noninvasive gene therapy in the future.
Gene Therapy 04/2007; 14(5):451-8. · 3.71 Impact Factor
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ABSTRACT: The study was undertaken to evaluate clinical and laboratory characteristics of patients with lupus enteritis and to investigate its association with anti-endothelial cell antibodies (AECAs). Systemic lupus erythematosus (SLE) patients who were admitted to Kangnam St. Mary's Hospital with complaints of acute abdominal pain from January 1990 to July 2006 were reviewed retrospectively. The clinical features, laboratory data and prognosis of these patients were analyzed. Among the 706 SLE patients admitted during the study period, 87 were found to admit for acute abdominal pain. Among them, 41 patients were identified with lupus enteritis. The SLE disease activity index score at admission and the mean prednisolone dose administered during the last three months prior to admission were significantly higher in patients with lupus enteritis than those with other causes (P < 0.001, P = 0.036). Serum anti-endothelial cell antibody (AECA-IgG) titer was also significantly higher in patients with lupus enteritis than those with other manifestations or healthy controls (P = 0.040, P < 0.001). Four out of 13 recurrent patients had pre-existing anti-phospholipid syndrome (APS), whereas only one out of 28 non-recurrent patients had pre-existing APS (P = 0.028). Most of the patients with lupus enteritis showed good response to high-dose intravenous steroids and there was no death directly associated with lupus enteritis.
Lupus 01/2007; 16(10):803-9. · 2.34 Impact Factor
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ABSTRACT: This study is designed to evaluate whether the PEGylated conjugated linoleic acid (PCLA) as the pro-drug can have favorable stability, bioavailability, and anti-adipogenic activity in 3T3-L1 cells for anti-obesity when compared with conjugated linoleic acid (CLA) itself. The CLA was simply coupled to poly(ethylene glycol) (PEG) at the melting state without solvents or catalysts through ester linkages between the carboxylic group of CLA and the hydroxyl group of PEG. To confirm of PCLA as the pro-drug, CLA release from PCLA was investigated by using high-performance liquid chromatographic (HPLC), showing that CLA release from PCLA was almost 90% in a nearly continuous fashion over the next 75h. Apoptosis was promoted by both CLA- and PCLA-treatments with increasing concentrations. However, the level of cell apoptosis induced by PCLA was lower than that induced by CLA owing to the biocompatible and hydrophilic properties of PEG. Moreover, the PCLA decreased glycerol-3-phosphate dehydrogenase (GPDH) activity in 3T3-L1 cells by acting upon major adipocyte marker proteins such as PPARgamma2, C/EBPalpha, and aP2 modulators. Furthermore, either CLA or PCLA stimulated basal, but not isoproterenol-sensitive, lipolysis in our cell model, suggesting that both CLA and PCLA may stimulate lipolysis via hormone sensitive lipase (HSL)-independent mechanisms. These results suggest that the PCLA may prove to be a stable pro-drug to control the deposition of fat in the human body, and that the anti-adipogenic effect of the PCLA on 3T3-L1 cells will offer a challenging approach for anti-obesity.
Archives of Biochemistry and Biophysics 01/2007; 456(1):19-29. · 2.93 Impact Factor
