• Title/Summary/Keyword: TGF-${\alpha}$

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Molecular Mechanisms of Microglial Deactivation by $TGF-{\beta}-inducible$ Protein ${\beta}ig-h3$

  • Kim, Mi-Ok;Lee, Eun-Joo H.
    • Animal cells and systems
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    • v.9 no.2
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    • pp.101-105
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    • 2005
  • [ ${\beta}ig-h3$ ] is a secretory protein that is induced by $TGF-{\beta}$ and implicated in various disease conditions including fibrosis. We have previously reported that ${\beta}ig-h3$ expression is implicated in astrocyte response to brain injury. In this study, we further investigated potential roles of ${\beta}ig-h3$ protein in the injured central nervous system (CNS). We specifically assessed whether the treatment of microglial cells with ${\beta}ig-h3$ can regulate microglial activity. Microglial cells are the prime effector cells in CNS immune and inflammatory responses. When activated, they produce a number of inflammatory mediators, which can promote neuronal injury. We prepared conditioned medium from the stable CHO cell line transfected with human ${\beta}ig-h3$ cDNA. We then examined the effects of the conditioned medium on the LPS- or $IFN-{\gamma}-mediated$ induction of proinflammatory molecules in microglial cells. Preincubation with the conditioned medium significantly attenuated LPS-mediated upregulation of $TNF-{\alpha},\;IL-1{\beta}$, iNOS and COX-2 mRNA expression in BV2 murine microglial cells. It also reduced $IFN-{\gamma}-mediated$ upregulation of $TNF-{\alpha}$ and COX-2 mRNA expression but not iNOS mRNA expression. Assays of nitric oxide release correlated with the mRNA data, which showed selective inhibition of LPS-mediated nitric oxide production. Although the regulatory mechanisms need to be further investigated, these results suggest that astrocyte-derived ${\beta}ig-h3$ may contribute to protection of the CNS from immune-mediated damage via controlling microglial inflammatory responses.

Effects of JaUmJeSeupTangKaKam (JUJSTK) on Atopic Dermatitis-like Skin Lesions in NC/Nga Mouse (아토피양(樣)피부염 NC/Nga생쥐에서 자음제습탕가감(滋陰除濕湯加減)의 투여가 피부염에 미치는 영향)

  • Lee, Nam-Yerl;Kim, Yun-Hee;Han, Jae-Kyung
    • The Journal of Pediatrics of Korean Medicine
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    • v.23 no.2
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    • pp.87-101
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    • 2009
  • Objectives : The purpose of this study is to investigate the effect of JUJSTK on atopic dermatitis in an in-vitro experiment using an NC/Nga atopic dermatitis mouse, which has histological and clinical similarities to the humans in terms of health condition. Methods : We evaluated IL-1$\beta$, IL-6, IL-10, TNF-$\alpha$ mRNA, TGF-$\beta$ mRNA, CD4+/IFN-$\gamma$+ and IL-17+CD4+Th17 cells of NC/Nga atopic dermatitis mouse by real-time PCR and intracellular staining in vitro. Results : JUJSTK medicines supressed the activities of IL-1$\beta$, IL-6, TNF-$\alpha$, TGF-$\beta$ mRNA and IL-17+CD4+Th17 cells and it incresed the activities of IL-10 mRNA in B cells. The level of CD4+/IFN-$\gamma$+ in T cells were increased by JUSSTK. Conclusions : JUJSTK on atopic dermatitis might be incredibly effective to the atopic dermatitis treatment.

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Effects of Kakamsodokum (KKSDU) on Atopic Dermatitis-like Skin Lesions in NC/Nga Mouse (아토피양(樣) 피부염 NC/Nga생쥐에서 가감소독음(加減消毒飮)의 투여가 피부염에 미치는 영향)

  • Song, Hyun-Jee;Han, Jae-Kyung;Kim, Yun-Hee
    • The Journal of Pediatrics of Korean Medicine
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    • v.23 no.1
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    • pp.23-35
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    • 2009
  • Objectives The purpose of this study is to investigate the effect of Kakamsodokum (KKSDU) on atopic dermatitis in an in-vitro experiment using an NC/Nga atopic dermatitis mouse, which has histological and clinical similarities to the condition in humans. Methods We evaluated $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, $TGF-{\beta}$, IL-10 mRNA, CD4+/$IFN-{\gamma}+$, and CD4+CD25+foxp3+ in B and T cells of NC/Nga atopic dermatitis mouse by real-time PCR and intracellular staining in vitro. Results KKSDU medicines supressed $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, $TGF-{\beta}$ mRNA and increased IL-10 mRNA in B cells. CD4+/$IFN-{\gamma}+$ and CD4+CD25+foxp3+ in T cells were increased by KKSDU. Conclusions KKSDU on atopic dermatitis might be very effective to the atopic dermatitis treatment.

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The Role of the Ethylacetate Fraction from Hydnocarpi Semen in Acute Inflammation In Vitro Model

  • Lee, Geum Seon;Shim, Hong;Lee, Ki-Man;Kim, Seung Hyun;Yim, Dongsool;Cheong, Jae Hoon;Kang, Tae Jin
    • IMMUNE NETWORK
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    • v.12 no.6
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    • pp.291-295
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    • 2012
  • We previously reported that Hydnocarpi Semen (HS) has a wound healing effect on diabetic foot ulcer lesion in mice. In this study, ethylacetate (EtOAc) fraction from HS extract were evaluated for their wound healing activity by using in vitro acute inflammation model. GC and GC/MS analysis shows that the main constituents in EtOAc fraction are chaulmoogric acid, hydnocarpic acid, and gorlic acid. EtOAc fraction activated macrophages to increase the production of TNF-${\alpha}$. The fraction also increased the production of TGF-${\beta}$ and VEGF, which induced fibroblast activation and angiogenesis. These results suggest that the mechanism that the fraction helps to enhance healing of skin wound is possibly associated with the production of TNF-${\alpha}$, as well as secretion of VEGF, TGF-${\beta}$ and HS may have a new bioactive material for the treatment of skin wound.

The Expression of Chemokine mRNAs in Musculoskeletal Tumors (근골격계 종양의 종류에 따른 케모카인 유전자의 발현)

  • Kim, Hee-Sun;Baik, Won-Jin;Lee, Won-Jae;Shin, Duk-Seop
    • The Journal of the Korean bone and joint tumor society
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    • v.9 no.2
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    • pp.178-189
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    • 2003
  • Purpose: The current study was designed to investigate the expression pattern of chemokine in musculoskeletal tumors, and between primary osteosarcoma and recurred, and postchemotherapy one. Materials and methods: Ten primary soft tissue and bone tumors, one primary, one recurred, one post-chemotherapy osteosarcoma, and one normal control patients were included in the current study. RT-PCR and RPA were used for the investigation of the expression of cytokines and chemokines. Fisher's exact test in SPSS was used for the statistical analysis. Results: IL-8 and TNF-${\alpha}$ were expressed in all tumor tissues, IFN-${\gamma}$ was in all except two cases, RANTES was in 5 soft tissue tumors and 4 bone tumors, GRO-${\alpha}$was in one soft tissue tumor and 2 bone tumors, and MCP-1 and IP-10 were in two bone tumors and in all the other group. In recurred osteosarcoma all the cytokines and chemokines were expressed, and the degree of the expression was stronger than the primary, except IFN-${\gamma}$. After chemotherapy, RANTES, IFN-${\beta}$ and TGF${\beta}_1$ among the TGF${\beta}$isoforms were expressed. Conclusion: There were differences in the expression of cytokines and chemokines in some different bone and soft tissue tumors, even though it was impossible to support this statistically due to small numbers of cases. The expression pattern of IFN-${\gamma}$and TGF-${\beta}$ isoform in osteosarcoma could be used for the study of tumor recurrence and the changes after chemotherapy.

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Effects of Sochungyong-tang on Cytokine Gene Expression in Mouse Alveolar Macrophage (소청용장(小靑龍湯)이 생쥐의 폐(肺) 대식세포(大食細胞) Cytokine 귀전자(遣傳子) 발현에 미치는 영향)

  • Park, In-Gi;Sim, Sung-Young;Byun, Hak-Sung;Kim, Kyung-Jun
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.18 no.3
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    • pp.1-17
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    • 2005
  • In many recent studies, molecular biological methods have been used to investigate the role of cytokines in pathogenesis of lung disease. This Experiment was conducted to investigate the effects of Sochungyong-tang on gene expressions in Mouse Alveolar Macrophage. Fer this purpose, we observed the cytokines ($IL-1{\beta}$, IL-6, IL-10, iNOS, $MIP-1{\alpha},\;MIP-1{\beta},\;MIP-1{\gamma},\;TGF-{\beta},\;TNF-{\alpha}$). We picked the alveolar macrophage out of mice and cultured it. We analyzed the cytokine gene expression by reverse transcription-PCR. The results obtained were as follows : 1 . Sochungyong-tang showed inhibitory effects on $IL-1{\beta}$ in time and concentration. 2. Sochungyong-tang showed inhibitory effects on IL-6 in time and concentration. 3. Sochungyong-tang showed inhibitory effects on IL-10 in concentration. 4. Sochungyong-tang showed inhibitory effects on iNOS. 5. Sochungyong-tang showed inhibitory effects on $TGF-{\beta}$ in time and concentration. 6. Sochungyong-tang showed on inhibitory effects on $MIP-1{\alpha},\;MIP-1{\beta},\;MIP-1{\gamma}$, $TCF-{\beta}$, $TNF-{\alpha}$. According to above results, it is supposed that Sochungyong-tang has the inhibitory effects on cytokine gene expression in mouse alveolar macrophage and can be usefully applied for curing inflammatory process of lung disease. Advanced studies are required to investigate the cure mechanism of Sochungyong-tang in the future.

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Effects of ChongMyung-Tang and ChongMyung-Tang added Moutan Cortex Hot water extract & Ultra-fine Powder on Microglia and Memory Deficit Model (총명탕(聰明湯)과 파극천총명탕(巴戟天聰明湯) 열수추출물, 초미세분말제형이 microglia 및 기억력 감퇴 병태모델에 미치는 영향)

  • Lim, Jung-Hwa;Jung, In-Chul;Lee, Sang-Ryong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.4
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    • pp.997-1008
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    • 2006
  • This experiment was designed to investigate the effect of the CMT and PCMT hot water extract & ultra-fine powder on microglia and memory deficit model. The effects of the CMT and PCMT hot water extract on expression of $IL-l{\beta},\;IL-6,\;TNF-{\alpha}$, NOS-II, COX-2, IL-10, $TGF-{\beta}1$ mRNA and production of $IL-l{\beta},\;IL-6,\;TNF-{\alpha}$, NO, ROS in BV2 microglial cell line treated by lipopolysacchaide(LPS) , serum glucose, uric acid, AChE activity of the memory deficit mice induced by scopolamine , behavior of the memory deficit mice induced by scopolamine and were investigated, respectively. The CMT and PCMT hot water extract suppressed the expression of $IL-l{\beta},\;IL-6,\;TNF-{\alpha}$, NOS-11, COX-2 mRNA, production of $IL-l{\beta},\;IL-6,\;TNF-{\alpha}$, NO, ROS and increased the expression of IL-10, $TGF-{\beta}1$ mRNA in BV2 microglial cell line treated by LPS. The PCMT hot water extract & ultra-fine powder increased glucose, decreased uric acid and AChE significantly in the serum of the memory deficit mice induced by scopolamine. The CMT and PCMT hot water extract & ultra-fine powder groups showed significantly inhibitory effect on the scopolamine-induced impairment of memory in the experiment of Morris water maze. According to the above result, it is suggested that the CMT and PCMT hot water extract & ultra-fine powder might be usefully applied for prevention and treatment of dementia.

Identification of MFGE8 in mesenchymal stem cell secretome as an anti-fibrotic factor in liver fibrosis

  • Jang, Yu Jin;An, Su Yeon;Kim, Jong-Hoon
    • BMB Reports
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    • v.50 no.2
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    • pp.58-59
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    • 2017
  • The beneficial paracrine roles of mesenchymal stem cells (MSCs) in tissue repair have potential in therapeutic strategies against various diseases. However, the key therapeutic factors secreted from MSCs and their exact molecular mechanisms of action remain unclear. In this study, the cell-free secretome of umbilical cord-derived MSCs showed significant anti-fibrotic activity in the mouse models of liver fibrosis. The involved action mechanism was the regulation of hepatic stellate cell activation by direct inhibition of the $TGF{\beta}$/Smad-signaling. Antagonizing the milk fat globule-EGF factor 8 (MFGE8) activity blocked the anti-fibrotic effects of the MSC secretome in vitro and in vivo. Moreover, MFGE8 was secreted by MSCs from the umbilical cord as well as other tissues, including teeth and bone marrow. Administration of recombinant MFGE8 protein alone had a significant anti-fibrotic effect in two different models of liver fibrosis. Additionally, MFGE8 downregulated $TGF{\beta}$ type I receptor expression by binding to ${\alpha}v{\beta}3$ integrin on HSCs. These findings revealed the potential role of MFGE8 in modulating $TGF{\beta}$-signaling. Thus, MFGE8 could serve as a novel therapeutic agent for liver fibrosis.

In Vitro Differentiation of Human Amniotic Membrane-derived Stem Cells into Hepatocyte-like Cells (양막 유래 줄기세포의 간세포로의 분화 유도)

  • Kook, Min-Ji;Park, Soo-Yeon;Kang, Hyun-Mi;Kim, Hae-Kwon
    • Development and Reproduction
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    • v.10 no.1
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    • pp.63-73
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    • 2006
  • This study aimed to find out suitable culture conditions for the differentiation of human amniotic membrane-derived stem cells(HAM) into hepatocyte-like cells. Almost homogenous population of fibroblast-like cells was successfully isolated from the amniotic membrane. In comparison to the non-coated plates and in the absence of insulin/transferrin/selenium(ITS), HAM cultured on the fibronectin-coated plates and in the presence of ITS showed the more intense immunocytochemical staining against the albumin. Addition of both fibroblast growth factor(FGF)-1 and -2 to the differentiation medium gave stronger staining compared to the treatment with FGF-1 or -2 alone. Periodic acid Schiff's base staining of glycogen and morphological turnover of fibroblast-like appearance of HAM into round shape matched the results of immunocytochemical studies. When the efficiency of two-step culture method was examined on the differentiation of HAM into hepatocyte-like cells, all of the results of immunocytochemical staining, periodic acid Schiff's staining and morphological change exhibited effective hepatic differentiation of HAM compared to the continuous culture method. Immunoblot analyses of HAM- conditioned media against the albumin showed that the culture of HAM in the presence of both ITS and fibronectin always gave a stronger staining intensity than those in the absence of them, and that the addition of ether mixture of FGF-4 and either FGF-2 or transforming growth $factor(TGF)-{\alpha}$ to the culture medium significantly enhanced the albumin secretion by HAM. Based on these observations, it is suggested that HAM could differentiate into hepatocyte-like cells under a culture condition consisting of fibronectin and ITS, and addition of FGF-4 with either one of FGF-2 or $TGF-{\alpha}$ could enhance the hepatic differentiation of HAM.

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IMMUNOHISTOCHEMICAL ASSAYS FOR THE EXPRESSION OF EPIDERMAL GROWTH FACTOR-SIGNALING PROTEINS IN ADENOID CYSTIC CARCINOMAS OF HUMAN SALIVARY GLANDS (타액선 선양낭성암종에서 상피성장인자 신호전달 단백의 발현에 관한 면역조직화학적 연구)

  • Park, Young-Wook;Kim, Jung-Hwan
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.28 no.6
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    • pp.499-510
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    • 2006
  • Malignant tumors of the human salivary glands may arise from major or minor salivary glands. Adenoid cystic carcinoma (ACC) is the second most common malignant neoplasm in the salivary glands. ACC is occasionally highly aggressive tumor that readily invades adjacent tissues and metastasize to distant organs at early stages of the disease. Although ACC tends to grow slowly, treatment outcome may be poor due to wide local infiltration, perineural or intraneural spread and a propensity for hematogenous metastasis. Therefore, knowledge of cellular and molecular characteristics that influence the growth, survival and metastasis of tumor cells, is important for new treatment strategies of salivary ACC. I determined expressions of epiderma growth factor (EGF)-signaling molecules using surgical specimens of human ACCs. Protein expressions of EGF, transforming growth $factor(TGF)-{\alpha}$, EGF receptor (EGFR), phosphorylated EGFR (pEGFR), and human EGF receptor (HER)-2 were assessed in 18 cases of salivary ACC by immunohistochemical staining. Adjacent normal salivary tissues and mucosal tissues, uninvolved by the malignant tumor, served as internal controls. Most of the tumors, especially ACC with a tubulocribriform pattern, were positive for EGF signaling molecules. The overall percentages of the 18 specimens expressing EGF, $TGF-{\alpha}$, EGFR, pEGFR, and HER2 were 50, 89, 61, 61 and 83% respectively. Moreover, tumor-associated endothelial cells and infiltrating immune-related cells in the stroma of ACC, also expressed these biomarkers. Taken together, EGF-signaling molecules are actively expressed in salivary ACC. Therefore, we suggest that these biomarkers can be molecular targets for new treatment strategies of salivary tumors.