• Journal of Life Science
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• v.22 no.2
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• pp.133-141
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• 2012

In this study, we established a radiodermatitis animal model and investigated the change in immune cell proportions in the secondary lymphoid organs. The cells responsible for the increased transforming growth factor-${\beta}1$ (TGF-${\beta}1$) and interleukin-10 (IL-10) production in the lesions following irradiation were also investigated. The radiodermatitis model was constructed by locally exposing the posterior dorsal region of hairless-1 (HR-1) mice to 10 Gy electron (E)-ray/day for six consecutive days. The change in immune cell proportions was analyzed by FACS. Immunohistochemistry was carried out to detect the expression of cytokines and cell-specific markers in the skin. The proportions of antigen-presenting cells, T cells, and B cells in the lymph nodes and spleen were affected by E-irradiation. After irradiation, TGF-${\beta}1$ and IL-17 were co-localized in the papillary region of the dermis with keratin-14 (K-14)-positive cells rather than with regulatory T cells (Treg). IL-10 was not co-stained with Treg, T helper 17 (Th17) cells, dendritic cells, or macrophages. Our data indicate that TGF-${\beta}1$ is over-expressed mainly by proliferated keratinocytes in the lesions of a radiodermatitis animal model.

• Journal of Microbiology and Biotechnology
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• v.23 no.7
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• pp.1023-1030
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• 2013

Lipoteichoic acid (LTA), uniquely expressed on gram-positive bacteria, is recognized by Toll-like receptor 2 (TLR2) on not only antigen-presenting cells but also activated T cells. Therefore, it is reasonable to assume that LTA is acting on T cells. However, little is known about the effect of LTA on T-cell regulation. In the present study, we investigated the immunomodulatory effects of LTA on $CD4^+$ T cells. Effector $CD4^+$ T cells, induced after co-culture with S. aureus-pulsed dendritic cells, produced high levels of interferon-${\gamma}$, CD25, CD69, and TLRs 2 and 4. When effector $CD4^+$ T cells were treated with LTA, the expressions of the membrane-bound form of transforming growth factor (TGF)-${\beta}$ and forkhead box P3 increased. Coincidently, the proliferation of effector $CD4^+$ T cells was declined after LTA treatment. When TGF-${\beta}$ signaling was blocked by the TGF-${\beta}$ receptor 1 kinase inhibitor, LTA failed to suppress the proliferation of effector $CD4^+$ T cells. Therefore, the present results suggest that LTA suppresses the activity of effector $CD4^+$ T cells by enhancing TGF-${\beta}$ production.

• Tuberculosis and Respiratory Diseases
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• v.79 no.4
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• pp.257-266
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• 2016

Background: Idiopathic pulmonary fibrosis is a common interstitial lung disease; it is a chronic, progressive, and fatal lung disease of unknown etiology. Over the last two decades, knowledge about the underlying mechanisms of pulmonary fibrosis has improved markedly and facilitated the identification of potential targets for novel therapies. However, despite the large number of antifibrotic drugs being described in experimental pre-clinical studies, the translation of these findings into clinical practices has not been accomplished yet. NADH:quinone oxidoreductase 1 (NQO1) is a homodimeric enzyme that catalyzes the oxidation of NADH to $NAD^+$ by various quinones and thereby elevates the intracellular $NAD^+$ levels. In this study, we examined the effect of increase in cellular $NAD^+$ levels on bleomycin-induced lung fibrosis in mice. Methods: C57BL/6 mice were treated with intratracheal instillation of bleomycin. The mice were orally administered with ${\beta}$-lapachone from 3 days before exposure to bleomycin to 1-3 weeks after exposure to bleomycin. Bronchoalveolar lavage fluid (BALF) was collected for analyzing the infiltration of immune cells. In vitro, A549 cells were treated with transforming growth factor ${\beta}1$ (TGF-${\beta}1$) and ${\beta}$-lapachone to analyze the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT). Results: ${\beta}$-Lapachone strongly attenuated bleomycin-induced lung inflammation and fibrosis, characterized by histological staining, infiltrated immune cells in BALF, inflammatory cytokines, fibrotic score, and TGF-${\beta}1$, ${\alpha}$-smooth muscle actin accumulation. In addition, ${\beta}$-lapachone showed a protective role in TGF-${\beta}1$-induced ECM expression and EMT in A549 cells. Conclusion: Our results suggest that ${\beta}$-lapachone can protect against bleomycin-induced lung inflammation and fibrosis in mice and TGF-${\beta}1$-induced EMT in vitro, by elevating the $NAD^+$/NADH ratio through NQO1 activation.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.314-320
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• 2000

Purpose :To investigate whether changes in plasma concentrations of transforming growth factor-$\beta$1(TGF-$\beta$1), tumor necrosis factor-alpha (TNF-$\alpha$) and interleukin-6 (IL-6) could be used to identify the development of radiation-induced pneumonitis in the lung cancer patients. Methods and Materials :Seventeen patients with lung cancer (11 NSCLC, 6 SCLC) were enrolled in a prospective study designed to evaluate clinical and molecular biologic correlation of radiation-induced pneumonitis. The study began in May 1998 and completed in July 1999. All patients were treated with radiotherapy with curative intent : 1.8 Gy per day, 5 fractions per week. Serial measurements of plasma TGF-$\beta$1, TNF-$\alpha$ and IL-6 were obtained in all patients before, weekly during radiotherapy and at each follow-up visits after completion of treatment. These measurements were quantified using enzyme linked immunosorbent assay (ELISA). All patients were evaluated for signs and symptoms of pneumonitis at each follow-up visit after completion of radiotherapy. High resolution CT (HRCT) scans were obtained when signs and symptoms of pneumonitis were developed after completion of radiotherapy. Results : Thirteen patients eventually developed signs and symptoms of clinical pneumonitis 씬file four patients did not. TGF-$\beta$ 1 levels were elevated in all 13 patients with pneumonitis, which showed characteristic pattern of elevation (38.45 ng/ml at pretreatment, 13.66 ng/ml during radiotherapy, then 60.63 ng/ml at 2-4 weeks after completion of radiotherapy). The levels of TNF- $\alpha$ and IL-6 were also elevated In the group of patients who developed pneumonitis but the pattern was not characteristic. Conclusions : Changes in plasma TGF$\beta$-1 levels before, during and after radiotherapy appears to be a useful means by which to identify patients at risk for the development of symptomatic pneumonitis. Other cytokines like TNF- $\alpha$ and IL-6 shows no meaningful changes in association with radiation pneumonitis.

• Development and Reproduction
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• v.4 no.1
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• pp.53-59
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• 2000

Endocrine disruptors (EDs) are exogenous chemicals which interfere several aspects of natural hormone properties. EDs with estrogenic activity have been recently reported to cause animal reproductive problems. This study was performed to investigate the effects of bisphenol A (BPA) on the mouse spermatogenesis in vivo. Male ICR mice were orally injected on a daily basis with low dose of BPA 20 mg/kg, high dose of BPA 200 mg/kg, or corn oil (vehicle control) for 7 days, and litter size and weights of body, testis, and cauda epididymis were measured. The level of serum testosterone and the expression of TGF- $\beta$$_1$ mRNA were also analyzed using RIA and RT-PCR, respectively. Also, morphological differences of testes after treatments were examined. Sperm concentration and level of serum testosterone showed a decreasing tendency detected as untreated >corn oil >low >high dose BPA treated mice, although there were no significant statistical differences. Interestingly, in mice treated with a high dose of BPA, partial disappearance of spermatozoa in seminiferous tubular lumen and the expression of TGF-$\beta$$_1$ mRNA were observed. Spermatogenesis was disrupted through TGF-$\beta$ system in the seminiferous tubules, resulting in no development of germ cells. Similarly, the litter size treated with a high dose of BPA was significantly different from that of untreated control group. In conclusion, these results that a high dose of BPA (200 mg/kg) acts as an endocrine disruptor during apermatogenesis in male mice md that there are BPA-specific lesions in the adult male reproductive tract might represent a permanently altered responsiveness to testosterone by BPA in the affected target tissue.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2003.10a
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• pp.142-142
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• 2003

• Proceedings of the Korean Society of Toxicology Conference
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• 2005.05a
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• pp.151-151
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• 2005

• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.5
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• pp.417-433
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• 2006

Purpose : Platelet rich plasma (PRP) is an autologous material with many growth factors, such as BMPs, PDGF, $TGF-{\beta}_1$, $TGF-{\beta}_2$, VEGF, and IGF, facilitating bone healing process. The prominent osteoconductive activity and the biodegradable nature of beta-tricalciumphosphate (${\beta}-TCP$) for bone grafts in animal experiments have been reported. The purpose of this study was to evaluate the effect of PRP on the osteogenesis of ${\beta}-TCP$. Materials & Methods : Two artificial calvarial bone defects were made in 32 rabbits which were divided into 2 groups. In one group of 16 rabbits, autogenous bone / ${\beta}-TCP$ was grafted on each side of cranial bone defect. In the other group of 16 rabbits, mixture of ${\beta}-TCP$ and PRP / PRP alone was grafted on each side of the cranial bone defect. The animals were sacrificed at 2, 4, 8, and 12 weeks after surgery. The specimens were harvested and examined histologically and immunohistochemically by the expression of BMP2/4/7, PDGF, VEGF and $TGF-{\beta}_1$. Results : The mean volume of new bone formation was significantly higher at 4, 8, 12 weeks in autogenous graft than that in ${\beta}-TCP$. The BMP2/4 expression was significantly higher at 4 weeks in autogenous bone graft and at 4 weeks in mixture of ${\beta}-TCP$ and PRP and at 12 weeks in ${\beta}-TCP$. The expression of BMP7, PDGF, VEGF and $TGF-{\beta}_1$ showed no significant difference in autogenous, ${\beta}-TCP$, mixture of ${\beta}-TCP$ and PRP, and PRP alone during grafted bone regeneration. Conclusion : The results showed that PRP had no additional value in promoting healing process of ${\beta}-TCP$ grafts.

• International Journal of Industrial Entomology and Biomaterials
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• v.5 no.2
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• pp.201-204
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• 2002

This study was undertaken to find effects of ethanol extracts from Bombyx mori on the hyperglycemia induced by streptozotocin in rats. Blood glucose level of rats increased depending on experimental days after streptozotocin treatment. But there was no difference in blood glucose level between the rats injected with ethanol extracts of B. mori and normal rats. There was no significant difference in the kidney fibrosis between the rats injected with ethanol extrscts of B. mori and normal rats at all ages examined. The transforming growth factor-$\beta$l ($TGF-{\beta}1$) protein was detected in the glomerulay endothelial cells and tubular epithelial cells of streptozotocin rats at 14 days of age. In the rats injected with ethanol extracts of B. mori to the kidneys, the $TGF-{\beta}1$ protein was detected very faintly. The $TGF-{\beta}1$ mRNA of streptozotocin rats increased at 14 days of age, and this was higher than the rats injected with ethanol extrscts of B. mori. Taken these together, the results suggest that the ethanol extracts of B. mori ameliorate hyperglycemia of the rats induced by streptozotocin.

• Proceedings of the KSAR Conference
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• 2003.06a
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• pp.94-94
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• 2003

Endocrine disrupters (EDs) are exogenous chemicals that interfere with the production, releasing, metabolism, excretion, binding of natural hormones, and whole endocrine systems. EDs are very dangerous since they are extremely stable, not easily degraded, and accumulated in fat and tissue. 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) is known as the most toxic EDs. Therefore, this study was conducted to investigate the effects of TCDD on proliferation of human breast cancer (MCF-7) and endometrial adenocarcinoma (Hec-1B) cells. 10, 100, and 1000 nM of TCDD were treated with steroid free condition. Viable cell counting, MTT, and BrdU assay was performed to investigate cell proliferation. Apoptosis was investigated using DNA laddering. Although, DNA fragmentation as the evidence of apoptosis was not detected, all of these cell lines showed restricted proliferation at 48 hrs after 100 and 1000 nM TCDD treatments. Recently, it has been reported that the expression of transforming growth factor $\beta$s (TGF-$\beta$s) are increased in TCDD treatment and also involved in regulation of cell cycle. Therefore, these results were considered that the decreased cell prolifcration by TCDD is related to the expression of TGF-$\beta$s.