• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.3
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• pp.199-203
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• 2007

Several matrix metalloproteinases (MMPs) have been shown to play an important role in the invasion and metastasis of oral squamous cell carcinoma (OSCC). The members of the TGF-$\beta$ signaling pathway are being considered as predictive biomarkers for progressive tumorigenesis and molecular targets for the prevention and the treatment of cancer and metastasis. The aim of the present study was to find the clinical significance of the expression of TGF-${\beta}1$ and MMP-2 related to the regional lymph node metastasis in OSCC. This study included 76 cases of primary OSCC, of which 42 cases showed regional lymph node metastases. Immunohistochemistry was used for the localization of protein. The relation between the expression of each protein and clinical variables was statistically evaluated. In results, the expression of TGF-${\beta}1$ both main mass with lymph node metastasis and without lymph node metastasis was found not to be statistically significant (p>0.05). The expression of MMP-2 was found to be statistically significant related to regional lymph node metastasis (p<0.05). When compared the expression in the metastatic lymph node, TGF-${\beta}1$ was significantly highly expressed than MMP-2 (p<0.05). In conclusion, the expression of MMP-2 was significantly elevated in patients with lymph node metastasis as compared to the patients without lymph node metastasis, which could be useful in predicting the risk of lymph node metastasis in OSCC.

• The Journal of Korean Physical Therapy
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• v.14 no.4
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• pp.87-94
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• 2002

Low intensity laser irradiation is potential physical agent that triggers the muscle regeneration by previous study. In muscle regeneration, a number of growth factors also promotes that is triggered in response to muscle damage. The transforming growth factor(TGF)-$\beta$ is involved in the activation of cell proliferation and the inhibition of cell differentiation in muscle regeneration. This is secreted not only autocrine system but also paracrine and endocrine. Therefore, We investigated that effects of Gallium aluminum arsenide(GaAlAs) diode laser for the expression of TGF-$\beta$ on lumbar spinal cord after extensor digitorum muscle crush injury. After laser irradiation, the immunoreactivity of TGF-$\beta$ was increased bilaterally in gray mater of spinal cord. Especially, in 1 day, experimental group was highed than control, and in 3 day, lateral motor nucleus were storong immunoreactivy of TGF-$\beta$. Also, in 1 and 2 day, TGF-$\beta$ was showed in white mater as well as gray mater, but in 3 day, only showed in gray mater. These data may suggests to the establishment of laser irradiation on spinal cord for skeletal muscle injury.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.27 no.2
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• pp.123-130
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• 2005

Many of the molecular and genotypic events taking place at the osteoblast cell level during bone-implant integration are still largely unknown. The objective of this study was to examine expression patterns of TGF-$\beta$ and IGF-I related genes during bone-implant integration. Titanium implants with machined surface were placed into 8 rabbit tibias. At 3rd, 7th, 14th, 28th day after implantation, the expression pattern of TGF-$\beta$ and IGF-I genes in bone with or without implant was examined using reverse transcriptase-polymerase chain reaction (RT-PCR). At the same time, histomorphometric analysis was evaluated, respectively. The bone-to-implant contacts (BIC) of experimental groups were 5.2%, 6.2%, 6.6%, 24.6% at 3rd, 7th, 14th, 28th day. This indicated that newly formed bone increased at the implant surface in bone marrow space after implantation. The expressions of TGF-$\beta$ and IGF-I were higher in implantation groups than untreated control groups during all experimental days. The increased expression of TGF-$\beta$ and IGF-I genes may be associated with the increased bone-to-implant contact. This result provided the evidence for existing biologic differences in tissue response after implantation and helped us to understand molecular biologic processes in tissue-implant integration.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.190-198
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• 2001

Purpose : It was reported that Captopril (angiotensin converting enzyme inhibitor) had an effect to reduce the pneumonitis and pulmonary fibrosis induced by radiation in rat. We peformed this study to investigate the radioprotective effect and mechanism of Captopril. Methods and Materials : The comparison was made between the radiation only group and the combined Captopril and radiation group by examining histopathologic findings and immunohistochemical stains $(TNF\alpha\;and\;TGF\beta1)$ at 2 and 8 weeks after irradiation. Each group has 8 to 10 rats (Sprague-Dawley). 12.5 Gy of X-ray was irradiated to the left hemithorax in a single fraction. Captopril (50 mg/kg/d) mixed with water was given per oral and continuously from 1 week prior to irradiation up to 8th week of the experiment. Result : In the combined Captopril and radiation group, the histopathologic changes which were hemorrhage into alveolar space, changes of alveolar epithelium, bronchial epithelium and blood vessels, and perivascular edema were less severe than in the radisation only group at 2 weeks. At 8 weeks, the alveolar epithelial changes and perivascular edema were less prominant in the combined Captopril and radiation group. At 2 weeks, the $TNF\alpha$ expression of the combined Captopril and radiation group was markedly decreased at the alveolar epithelium (p<0.01), lymphoid tissue (p=0.06) and the macrophage of alveolar space (p<0.01) compared with the radiation only group. Furthermore the $TGF\beta1$ expression was significantly prominant at the alveolar epithelium (p<0.02) and the macrophage in alveolar space (p<0.02). At 8 weeks, the expression of $TNF\alpha\;and\;TGF\beta1$ of most sites, except $TGF\beta1$ of the macrophage of alveolar space (p=0.09), showed no significant difference between 2 groups. Conclusion : This study revealed that early lung damage induced by irradiation was reduced with the addition of Captopril in the latent and early pneumonitis phase. The expression of $TNF\alpha\;and\;TGF\beta1$ at 2 weeks and $TGF\beta1$ at 8 weeks was further decreased in the combined Captopril and radiation group than the radiation only group. From these results, it may be concluded that the proinflammatoy cytokine $(TNF\alpha)$ and fibrogenic cytokine $(TGF\beta1)$ probably play the role of the radioprotective mechanism in Captopril.

• Tuberculosis and Respiratory Diseases
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• v.70 no.3
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• pp.206-217
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• 2011

Background: Transcription factor FOXP3 characterizes the thymically derived regulatory T cells. FOXP3 is expressed by cancer cell itself and FOXP3 expression was induced by TGF-${\beta}$ treatment in pancreatic cancer cell line. However, the expression of FOXP3 expression is not well known in patients with lung cancer. This study was conducted to investigate the expression of FOXP3 in patients with lung cancer and to investigate the regulation of FOXP3 expression by the treatment of TGF-${\beta}$ and DNA methyltransferase inhibitor in lung cancer cell lines. Methods: FOXP3 expression in the tissue of patients with resected non-small cell lung cancer (NSCLC) was evaluated by immunohistochemistry. The regulation of FOXP3 expression was investigated by Western blot and RT-PCR after lung cancer cell lines were stimulated with TGF-${\beta}1$ and TGF-${\beta}2$. The regulation of FOXP3 expression was also investigated by RT-PCR and flow cytometry after lung cancer cell lines were treated with DNA methyltransferase inhibitor (5-AZA-dC). Results: FOXP3 expression was confirmed in 27% of patients with NSCLC. In NCI-H460 cell line, TGF-${\beta}2$ decreased FOXP3 mRNA and protein expressions. In A549 cell line, both TGF-${\beta}1$ and TGF-${\beta}2$ decreased FOXP3 mRNA and protein expressions. 5-AZA-dC increased FOXP3 mRNA expression in NCI-H460 and A549 cell lines. Moreover, 5-AZA-dC increased intracellular FOXP3 protein expression in A549 cell lines. Conclusion: It was shown that FOXP3 is expressed by cancer cell itself in patients with NSCLC. Treatment of TGF-${\beta}2$ and DNA methyltransferase inhibitor seems to be associated with the regulation of FOXP3 expression in lung cancer cell lines.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5181-5186
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• 2014

Tumors have evolved numerous mechanisms by which they can escape from immune surveillance. One of these is to produce immunosuppressive cytokines. Transforming growth factor-${\beta}$(TGF-${\beta}$) is a pleiotropic cytokine with a crucial function in mediating immune suppression, especially in the tumor microenvironment. TGF-${\beta}$ produced by T cells has been demonstrated as an important factor for suppressing antitumor immune responses, but the role of tumor-derived TGF-${\beta}$ in this process is poorly understood. In this study, we demonstrated that knockdown of tumor-derived TGF-${\beta}$ using shRNA resulted in dramatically reduced tumor size, slowing tumor formation, prolonging survival rate of tumor-bearing mice and inhibiting metastasis. We revealed possible underlying mechanisms as reducing the number of myeloid-derived suppressor cells (MDSC) and $CD4^+Foxp3^+$ Treg cells, and consequently enhanced IFN-${\gamma}$ production by CTLs. Knockdown of tumor-derived TGF-${\beta}$ also significantly reduced the conversion of na$\ddot{i}$ve $CD4^+$ T cells into Treg cells in vitro. Finally, we found that knockdown of TGF-${\beta}$ suppressed cell migration, but did not change the proliferation and apoptosis of tumor cells in vitro. In summary, our study provided evidence that tumor-derived TGF-${\beta}$ is a critical factor for tumor progression and evasion of immune surveillance, and blocking tumor-derived TGF-${\beta}$ may serve as a potential therapeutic approach for cancer.

• IMMUNE NETWORK
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• v.14 no.1
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• pp.30-37
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• 2014

Collaboration of TLR and non-TLR pathways in innate immune cells, which acts in concert for the induction of inflammatory cytokines, can mount a specific adaptive immune response tailored to a pathogen. Here, we show that murine DC produced increased IL-23 and IL-6 when they were treated with LPS together with curdlan that activates TLR4 and dectin-1, respectively. We also found that the induction of the inflammatory cytokine production by LPS and curdlan requires activation of IKK. However, the same treatment did not induce DC to produce a sufficient amount of TGF-${\beta}$. As a result, the conditioned media from DC treated with LPS and curdlan was not able to direct $CD4^+$ T cells to Th17 cells. Addition of TGF-${\beta}$ but not IL-6 or IL-$1{\beta}$ was able to promote IL-17 production from $CD4^+$ T cells. Our results showed that although signaling mediated by LPS together with curdlan is a potent stimulator of DC to secrete many pro-inflammatory cytokines, TGF-${\beta}$ production is a limiting factor for promoting Th17 immunity.

• Tuberculosis and Respiratory Diseases
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• v.82 no.1
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• pp.42-52
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• 2019

Background: Transforming growth factor ${\beta}$ (TGF-${\beta}$), retinoic acid (RA), p38 mitogen-activated protein kinase (MAPK), and MEK signaling play critical roles in cell differentiation, proliferation, and apoptosis. We investigated the effect of RA and the role of these signaling molecules on the phosphorylation of Smad2/3 (p-Smad2/3) induced by TGF-${\beta}1$. Methods: A549 epithelial cells and CCD-11Lu fibroblasts were incubated and stimulated with or without all-trans RA (ATRA) and TGF-${\beta}1$ and with MAPK or MEK inhibitors. The levels of p-Smad2/3 were analyzed by western blotting. For animal models, we studied three experimental mouse groups: control, bleomycin, and bleomycin+ATRA group. Changes in histopathology, lung injury score, and levels of TGF-${\beta}1$ and Smad3 were evaluated at 1 and 3 weeks. Results: When A549 cells were pre-stimulated with TGF-${\beta}1$ prior to RA treatment, RA completely inhibited the p-Smad2/3. However, when A549 cells were pre-treated with RA prior to TGF-${\beta}1$ stimulation, RA did not completely suppress the p-Smad2/3. When A549 cells were pre-treated with MAPK inhibitor, TGF-${\beta}1$ failed to phosphorylate Smad2/3. In fibroblasts, p38 MAPK inhibitor suppressed TGF-${\beta}1$-induced p-Smad2. In a bleomycin-induced lung injury mouse model, RA decreased the expression of TGF-${\beta}1$ and Smad3 at 1 and 3 weeks. Conclusion: RA had inhibitory effects on the phosphorylation of Smad induced by TGF-${\beta}1$ in vitro, and RA also decreased the expression of TGF-${\beta}1$ at 1 and 3 weeks in vivo. Furthermore, pre-treatment with a MAPK inhibitor showed a preventative effect on TGF-${\beta}1$/Smad phosphorylation in epithelial cells. As a result, a combination of RA and MAPK inhibitors may suppress the TGF-${\beta}1$-induced lung injury and fibrosis.

• Clinical and Experimental Reproductive Medicine
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• v.38 no.4
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• pp.210-215
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• 2011

Objective: This study was performed to identify whether growth and differentiation factor-9 (GDF-9) and transforming growth factor-${\beta}1$ (TGF-${\beta}1$) expressions would be lower in the follicular fluid (FF) of those over age 35 who underwent IVF than under age 35. Methods: A total of 24 IVF cycles (20 patients) were included in this study. All of patients were stimulated for IVF by the GnRH short protocol and divided into two groups for analysis, according to their age: <35 group (14 cycles, 11 patients) vs. ${\geq}35$ group (10 cycles, 9 patients). The expression levels of GDF-9 and TGF-${\beta}1$ were determined by western blotting and quantitative enzyme-linked immunosorbent assay. Results: The numbers of retrieved oocytes and metaphase II oocytes were significantly lower in the ${\geq}35$ group. Lower expression of GDF-9 and TGF-${\beta}1$ by western blotting in the ${\geq}35$ group were observed as well. The mean GDF-9 and TGF-${\beta}1$ levels by enzyme-linked immunosorbent assay were lower in the ${\geq}35$ group. The values were $6,850.5{\pm}928.4$ ng/L vs. $3,333.3{\pm}1,089.2$ ng/L of GDF-9 ($p$ <0.05) and $3,844.1{\pm}571.1$ ng/L vs. $2,187.7{\pm}754.0$ ng/L of TGF-${\beta}1$ ($p$ <0.05). A negative correlation between GDF-9 and age was observed (r=-0.546, $p$=0.006). Conclusion: GDF-9 and TGF-${\beta}1$ production from stimulated ovaries during IVF appears to decrease with age.

• Korean Journal of Biological Psychiatry
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• v.13 no.1
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• pp.32-37
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• 2006

Background : Several studies have suggested that alterations of cytokine level could be related to the pathophysiology of bipolar disorder. In this study, we measured plasma level of Interleukin-12(IL-12), a pro-inflammatory cytokine and transforming growth factor-${\beta}$1(TGF-${\beta}$1), an anti-inflammatory cytokine before and after treatment in acute manic patients. Methods : The plasma concentrations of IL-12 and TGF-${\beta}$1 were measured using quantitative ELISA in 18 bipolar disorder patients and 25 normal controls at admission and 6 weeks later. The psychopathology was measured by Brief Psychiatric Rating Scale(BPRS) and Young Mania Rating Scale(YMRS). Results : IL-12 levels were significantly higher in bipolar manic patients than in controls before treatment. Following the 6-week treatment, the IL-12 level was decreased than before treatment, but sustained still higher level than normal control. TGF-${\beta}$1 level was not significant different between manic patients and normal controls before treatment, but was increased after treatment comparing with before treatment in bipolar patients. The ratio of IL-12 and TGF-${\beta}$1 was significantly decreased after treatment. Conclusion : Cytokine abnormalities in bipolar disorder might be involved in the pathophysiology of the illness. It is possible that TGF-${\beta}$1 plays an important role in the regulation of immunological imbalance in bipolar disorder.