• IMMUNE NETWORK
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• 제9권4호
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• pp.122-126
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• 2009

Transforming growth factor-$\beta$ (TGF-$\beta$) is a highly pleiotropic cytokine playing pivotal roles in immune regulation. TGF-$\beta$ facilitates tumor cell survival and metastasis by targeting multiple cellular components. Focusing on its immunosuppressive functions, TGF-$\beta$ antagonists have been employed for cancer treatment to enhance tumor immunity. TGF-$\beta$ antagonists exert anti-tumor effects through #1 activating effector cells such as NK cells and cytotoxic $CD8^+$ Tcells (CTLs), #2 inhibiting regulatory/suppressor cell populations, #3 making tumor cells visible to immune cells, #4 inhibiting the production of tumor growth factors. This review focuses on the effect of TGF-$\beta$ on T cells, which are differentiated into effector T cells or newly identified tumor-supporting T cells.

• 대한본초학회지
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• 제28권4호
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• pp.49-55
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• 2013

Objectives : Mori Folium was popularly used as one of the traditional medicinal herbs. Although M. Folium has been cultivated for rearing silkworm historically, it's use has been expanded as natural therapeutic agent for the treatment of filariasis, diabetes and dropsy in East Asia. However, little has been known about the effect of M. Folium on liver fibrosis. Therefore, we would like to explore an anti-fibrogenic potential of M. Folium extract (MFE) using immortalized human hepatic stellate cell line, LX-2 cells. Methods : We examined the effects of MFE on the transforming growth factor ${\beta}1$ ($TGF{\beta}1$)-induced liver fibrosis in LX-2 cells. Cell viability, Smad binding element-driven luciferase activity, phosphorylations level of Smad 2/3, and expression level of $TGF{\beta}1$-dependent target genes were monitored in the MFE-treated LX-2 cells. Results : Up to 30 ${\mu}g/ml$ MFE treatment did not show any possible toxic effect in LX-2 cells. MFE inhibited $TGF{\beta}1$-inducible Smad binding element-driven luciferase activity and decreased the $TGF{\beta}1$-inducible phosphorylations of Smad 2 and Smad 3 in hepatic stellate cell in a dose dependent manner. Furthermore, increases of plasminogen activator inhibitor type 1, $TGF{\beta}1$ and matrix metalloproteinases 2 genes by $TGF{\beta}1$ were also attenuated by MFE treatment. Conclusions : These findings suggested that MFE would be used as a potential therapeutic agent for the treatment liver fibrosis, which might be mediated by the inhibition of $TGF{\beta}1$-inducible Smad 2/3 transactivation and target genes expression.

• 대한한의학회지
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• 제22권3호
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• pp.141-155
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• 2001

Objective : The aim of this study is to investigate the effect of Injin fractions on hepatic fibrosis induced by $TGF-{\beta}1$. Method : $TGF-{\beta}1$ mRNA, protein, $TGF-{\beta}1$ receptor, Smad family and PAI-I mRNA were studied in HepG2 cell, and the proliferation, connective tissue growth factor, fibronectin and collagen type I mRNA in T3891 fibroblast by quantitative RT-PCR, ELISA and thymidine incorporation assay. Results : On $TGF-{\beta}1$ mRNA and protein synthesis in HepG2, $H_2O$, butanol and hexane fractions of Injin showed inhibitory effect in a dose-dependent way. In the study on $TGF-{\beta}1$ receptor, Smad family and PAI-1 mRNA in HepG2, $H_2O$, butanol and hexane fraction of Injin showed inhibitory effect on the expression of PAI-1 in a dose-dependent way. On the proliferation of T3891 fibroblast induced by $TGF-{\beta}1$, $H_2O$, ethylacetate and butanol fractions of Injin showed inhibitory effect. In the study on the factors affected by $TGF-{\beta}1$, $H_2O$, ethylacetate and butanol fractions of Injin showed inhibitory effect on CTGF, and $H_2O$, butanol, chloroform and hexane fractions showed inhibitory effect on the expression of collagen type I, whereas no fraction showed inhibitory effect on the expression of fibronectin Conclusion : These results show that each fraction of Injin acts as a fibrosis inhibitory factor by itself or in combination, ultimately inhibiting liver cirrhosis.

• Tuberculosis and Respiratory Diseases
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• 제70권3호
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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.

• 한국동물학회지
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• 제38권1호
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• pp.20-25
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• 1995

계배 limb bud 간충직 연골원성 세포로부터 연골세포로의 분화에 미치는 transforming growth factor-f2(TGF-$\beta$2)의 영향을 알아보기 위하여, Hamburger-Hamilton stages 23/24의 간충직 세포들을 미세배양법으로 배양하면서. TGF-$\beta$2의 농도 및 처리시간에 따른 연골세포의 분화에 미치는 영향을 조사하였다 그 결과 TGF-$\beta$2는 배양 첫 24시간 동안 1-2 ng/ml의 농도로 처리하였을 때 가장 효과적으로 연골세포의 분화를 촉진하였으며, 또한 TGF-$\beta$2의 처리군에서 배양 3일째에 tsss) sulfate의 glycosaminoglvcan으로의 유입량이 현저히 증가함을 보였다 한편. 배양 48시간내에TGF-$\beta$2를 처리한 경우 분화를 촉진 유도한 반면, 배양 48시간 이후에 처리하였을 때에는 분화 촉진 효과가 나타나지 않았다. 이상의 결과로부터 TGF-$\beta$2는 연골원 세포의 분화 초기단계에 세포외기질의 합성을 촉진시켜 세포응축을 유발하고. 세포-세포 및 세포-세포외기질의 상호작용을 증대시킴으로써 연골세포로의 분화를 촉진시킬 것으로 추정되었다.

• The Korean Journal of Physiology and Pharmacology
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• 제5권4호
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• pp.353-357
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• 2001

The pathogenesis of the nasal polyp is multifactorial and choanal polyps can be defined by its origin of genesis: antrochoanal (maxillochoanal), ethmochoanal and sphenochoanal polyp. Transforming growth $factor-{\beta}\;(TGF-{\beta})$ has various biologic activities, including the regulation of epithelial proliferation, the promotion of extracellular matrix formation and the induction of angiogenesis, hence closely related to pathogenesis of nasal polyp. Twenty cases of choanal polyps (13 antrochoanal, 4 ethmochoanal and 3 sphenochoanal polyps) were included in this study. Each polyp was subdivided into its origin, pedicle and choanal part. Hematoxylin and eosin stain for routine histopathology and immunohistochemistry were employed to detect expression of $TGF-{\beta}1.$ According to polyp type, edematous type is common at origin part and fibrous type at choanal part, and showed no difference at pedicle part in frequency. In ethmochoanal and sphenochoanal polyps, glandulocystic and edematous type is more common than fibrous type. $TGF-{\beta}1$ was expressed in epithelial cells, endothelial cells, eosinophils and lymphocytes. There was no different expression of $TGF-{\beta}1$ in each kind of choanal polyps and separate parts in each polyp. But histologic finding of choanal polyp is different between origin, pedicle and choanal part. Also infiltration of inflammatory cells including eosinophils has no difference between origin site. The expression of $TGF-{\beta}1$ was observed at all the choanal polyps and no difference between origin site and each portions was noted.

• 대한한의학방제학회지
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• 제26권3호
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• pp.183-193
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• 2018

Objectives : In Traditional Korean Medicine, Epimedium koreanum Nakai has diverse pharmacological activities to treat impotence, forgetfulness, cataract and exophthalmos. Present study investigated anti-fibrogenic effects of E. koreanum water extract (EKE) in hepatic stellate cells (HSCs). Methods : To study anti-fibrogenic effects of EKE, LX-2 cells, a human immortalized HSCs, were pre-treated with $3-300{\mu}g/mL$ of EKE, and then subsequently exposed to 5 ng/mL of transforming growth $factor-{\beta}1$ ($TGF-{\beta}1$). Expression level of ${\alpha}-smooth$ muscle actin was determined by immunoblot analysis. Phosphorylation of Smad, transactivation of Smad, and expression of plasminogen activator inhibitor-1 (PAI-1) were monitored to investigate the effect of EKE on $TGF-{\beta}1-mediated$ signaling pathway. Results : Up to $100{\mu}g/mL$, EKE did not show any cytotoxicity on LX-2 cells. Pre-treatment of EKE ($100{\mu}g/mL$) significantly inhibited ${\alpha}-smooth$ muscle actin expression induced by $TGF-{\beta}1$. In addition, EKE significantly decreased Smad2 and Smad3 phosphorylations, Smad binding element-driven luciferase activity and PAI-1 expression by $TGF-{\beta}1$. Of three flavonoid compounds found in EKE, only quercertin ($30{\mu}M$) attenuated $TGF-{\beta}1-mediated$ PAI-1 expression. Conclusion : These results suggest that EKE has an ability to suppress fibrogenic process in HSCs via inhibition of $TGF-{\beta}1/Smad$ signaling pathway.

• Clinical and Experimental Reproductive Medicine
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• 제35권1호
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• pp.49-60
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• 2008

목 적: 자궁내막조직에서 분리한 상피세포와 기질세포를 삼차원 공배양을 통한 탈락막화 유도에서 성호르몬과 TGF-${\beta}1$의 역할을 알아보고 2-세포기 생쥐배아와 탈락막화가 유도된 자궁내막세포와의 공배양을 통하여 포배형성율, 부화율, 포배기배아의 내세포괴와 영양막세포수 및 부착율을 알아보기 위해 시행되었다. 연구방법: 인간 자궁내막조직에서 분리된 기질세포와 상피세포의 표지인자인 cytokeratin과 vimentin에 대한 면역조직 화학염색을 실시하여 분리를 확인하였으며, 성호르몬 우세환경 (progesterone, estrogen)에서 분리된 세포를 단일배양 혹은 3차원 공배양을 통하여 RT-PCR법으로 TGF-${\beta}1$, 수용체-1, -2, integrin-${\beta}3$, prolactin의 발현을 조사하였다. 배양액군을 대조군으로 하여 2-세포기 생쥐배아와 탈락막화 유도와 유도하지 않은 인간 자궁내막세포와의 공배양을 통하여 포배형성율, 부화율, 부착율과 부화된 포배의 영양막세포와 내세포괴수를 비교하였다. 결 과: 상피세포 표지인자인 cytokeratin과 기질세포 표지인자인 vimentin을 이용하여 면역조직화학염색을 한 결과 각각 95% 이상에서 양성반응을 나타내어 자궁내막조직으로부터 상피세포와 기질세포가 성공적으로 분리되었음을 확인하였다. 분리된 상피세포와 기질세포를 단일배양에서는 성호르몬의 조건에 관계없이 TGF-${\beta}1$과 수용체 type-1, type-2, integrin-${\beta}3$, prolactin mRNA가 발현되지 않았다. 공배양에서는 progesterone 우세환경일 경우 TGF-${\beta}1$ 수용체 type-2를 제외한 모든 mRNA가 발현하였으나 estrogen 우세환경에서는 TGF-${\beta}1$ 수용체 type-2와 prolactin이 발현되지 않았다. 2-세포기 생쥐배아를 배양액군, 비탈락막군 및 탈락막군으로 나누어 공배양하였을 때 포배기 발달율은 차이가 없었으나 부화율 (92%)과 부착율 (82%)은 탈락막군이 유의하게 높았으며 (p<0.05), 비탈락막군의 공배양에서 다수의 영양막세포가 투명대를 완전히 빠져나오지 않은 상태로 부착한 비정상형태를 보였다. 부화된 생쥐 포배기배아의 내세포괴수는 탈락막화에 관계없이 공배양한 포배의 내세포괴수가 유의하게 많았으며 (p<0.05), 영양막세포수는 탈락막군에서 배양액군과 비탈락막군보다 유의하게 많았다 (p<0.05). 결 론: 자궁내막조직에서 상피세포와 기질세포를 분리하여 다시 삼차원적 공배양을 통하여 progesterone (100 nM), estrogen (1 nM)과 TGF-${\beta}1$ (10 ng/ml)을 첨가하면 체외에서 탈락막화를 유도할 수 있으며, 탈락막화를 유도한 자궁내막 세포와 2-세포기 생쥐배아를 공배양하였을 때 탈락막화가 부화율, 부착율 및 영양막세포수에 유효한 영향을 미치는 것을 알 수 있었다.

• Asian-Australasian Journal of Animal Sciences
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• 제32권4호
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• pp.477-484
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• 2019

Objective: We aimed to observe hair follicle (HF) development in the dorsal skin and elucidate the expression patterns of genes and proteins related to skin and HF development in Rex rabbits from birth to 8 weeks of age. Methods: Whole-skin samples were obtained from the backs of Rex rabbits at 0, 2, 4, 6, and 8 weeks of age, the morphological development of primary and secondary HFs was observed, and the gene transcript levels of insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF), bone morphogenetic protein 2 (BMP2), transforming growth factor ${\beta}-1$, 2, and 3 ($TGF{\beta}-1$, $TGF{\beta}-2$, and $TGF{\beta}-3$) were examined using quantitative real-time polymerase chain reaction (PCR). Additionally, Wnt family member 10b (Wnt10b) and ${\beta}$-Catenin gene and protein expression were examined by quantitative real-time PCR and western blot, respectively. Results: The results showed significant changes in the differentiation of primary and secondary HFs in Rex rabbits during their first 8 weeks of life. The IGF-I, EGF, $TGF{\beta}-2$, and $TGF{\beta}-3$ transcript levels in the rabbits were significantly lower at 2 weeks of age than at birth and gradually increased thereafter, while the BMP2 and $TGF{\beta}-1$ transcript levels at 2 weeks of age were significantly higher than those at birth and gradually decreased thereafter. ${\beta}$-Catenin gene expression was also significantly affected by age, while the Wnt10b transcript level was not. However, the Wnt10b and ${\beta}$-catenin protein expression levels were the lowest at 2 and 4 weeks of age. Conclusion: Our data showed that a series of changes in HFs in dorsal skin occurred during the first 8 weeks. Many genes, such as IGF-I, EGF, BMP2, $TGF{\beta}-1$, $TGF{\beta}-2$, $TGF{\beta}-3$, and ${\beta}$-Catenin, participated in this process, and the related proteins Wnt10b and ${\beta}$-Catenin in skin were also affected by age.

• Journal of Periodontal and Implant Science
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• 제47권2호
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• pp.66-76
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• 2017

Purpose: Oral wound healing requires gingival fibroblasts to respond to local growth factors. Epigenetic silencing through DNA methylation can potentially decrease the responsiveness of gingival fibroblasts to local growth factors. In this study, our aim was to determine whether the inhibition of DNA methylation sensitized gingival fibroblasts to transforming growth factor-${\beta}1$ (TGF-${\beta}1$). Methods: Gingival fibroblasts were exposed to 5-aza-2'-deoxycytidine (5-aza), a clinically approved demethylating agent, before stimulation with TGF-${\beta}1$. Gene expression changes were evaluated using quantitative polymerase chain reaction (PCR) analysis. DNA methylation was detected by methylation-sensitive restriction enzymes and PCR amplification. Results: We found that 5-aza enhanced TGF-${\beta}1$-induced interleukin-11 (IL11) expression in gingival fibroblasts 2.37-fold (P=0.008). 5-aza had no significant effects on the expression of proteoglycan 4 (PRG4) and NADPH oxidase 4 (NOX4). Consistent with this, 5-aza caused demethylation of the IL11 gene commonly next to a guanosine (CpG) island in gingival fibroblasts. The TGF-${\beta}$ type I receptor kinase inhibitor SB431542 impeded the changes in IL11 expression, indicating that the effects of 5-aza require TGF-${\beta}$ signaling. 5-aza moderately increased the expression of TGF-${\beta}$ type II receptor (1.40-fold; P=0.009), possibly enhancing the responsiveness of fibroblasts to TGF-${\beta}1$. As part of the feedback response, 5-aza increased the expression of the DNA methyltransferases 1 (DNMT1) (P=0.005) and DNMT3B (P=0.002), which are enzymes responsible for gene methylation. Conclusions: These in vitro data suggest that the inhibition of DNA methylation by 5-aza supports TGF-${\beta}$-induced IL11 expression in gingival fibroblasts.