• Title/Summary/Keyword: TGF-{\beta}

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The experimental Studies on the immunomodulational effects of Lonicerae Caulis et Folium -the effects of Lonicerae Caulis et Folium on cytokines production in mice splenocytes- (인동등(忍冬藤)의 면역조절작용(免疫調節作用)에 대한 실험적(實驗的) 연구(硏究)(II) -인동등(忍冬藤) 각 fraction이 mice 비장세포에서 cytokines 생성에 미치는 영향-)

  • Lee, Young-Cheol;Kwon, Taek-Hyun;Ok, In-Soo;Seo, Chang-Woo;Kim, Yang-Jin;Roh, Seong-Soo;Seo, Young-Bae
    • The Korea Journal of Herbology
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    • v.20 no.4
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    • pp.141-149
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    • 2005
  • In order to investigate the immunomodulational effects of Lonicerae Caulis et Folium, the author measured cytokines production(IL-10, IL-12(P35), IL12(P40), $IFN-{\gamma}$) in mice splenocytes. The results were obtained as follows : 1. The water extract of Lonicerae Caulis et Folium significantly enhanced the gene expression of IL-12(P35), IL-12(P40), but reduced the gene expression of IL-10, $IFN-{\gamma}$. 2. In water fraction and ethyl acetate fraction, the gene expression of IL-12(P35), $IFN-{\gamma}$ was significantly increased and that of IL-12(P40), IL-10 was decreased. The above results demonstrate that Lonicerae Caulis et Folium has enhancing immune activity by upregulation of these cytokines. Therefore, if we make the relationship between these cytokines(IL-10, IL-12, $IFN-{\gamma}$) besides IL-1, IL-4, IL-6, $TNF-{\alpha}$, IL-8, $TGF-{\beta}$ and so on which concerned the immunopotentiation, the immunopotentiational mechanism of Lonicerae Caulis et Folium will be shown clearly.

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Smad4 mediates malignant behaviors of human ovarian carcinoma cell through the effect on expressions of E-cadherin, plasminogen activator inhibitor-1 and VEGF

  • Chen, Chen;Sun, Ming-Zhong;Liu, Shuqing;Yeh, Dongmei;Yu, Lijun;Song, Yang;Gong, Linlin;Hao, Lihong;Hu, Jun;Shao, Shujuan
    • BMB Reports
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    • v.43 no.8
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    • pp.554-560
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    • 2010
  • Smad4 is involved in cancer progression and metastasis. Using a pair of human syngeneic epithelial ovarian cancer cells with low (HO-8910) and high (HO-8910PM) metastatic abilities, we aimed to reveal the role of Smad4 in ovarian cancer metastasis in vitro. Smad4 was down-regulated in HO-8910PM cell line relative to HO-8910 by implicating Smad4 was probably a potential tumor suppressor gene for ovarian cancer. Re-expression of Smad4 decreased the migration ability and inhibited the invasion capacity of HO-8910PM, while promoted the cell adhesion capacity for HO-8910PM. The stable expression of Smad4 increased the expression of E-cadherin, reduced the expression of plasminogen activator inhibitor-1 (PAI-1) and slightly down-regulated the expression of VEGF. Smad4 suppresses human ovarian cancer cell metastasis potential through its effect on the expressions of PAI-1, E-cadherin and VEGF. Results from current work implicate Smad4 might suppress the invasion and metastasis of human ovarian tumor cells through a TGF-$\beta$/Smad-mediated pathway.

Anti-apoptotic Effects of House Dust Mite, S100A8 and S100A9 on Spontaneous Apoptosis of Neutrophils in Coculture with Immune Cells and in the Presence of T Helper Cytokines

  • Kim, In Sik;Lee, Ji-Sook
    • Biomedical Science Letters
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    • v.21 no.2
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    • pp.122-125
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    • 2015
  • House dust mite (HDM) as a major allergen and damage-associated molecular pattern (DAMP) such as S100A8 and S100A9 trigger the pathogenesis and severity of allergic disease such as asthma. Regulation of neutrophil apoptosis is an important immune response and its dysregulation is involved in pathogenesis of allergic diseases. In this study, we examined the effects of HDM, S100A8 and S100A9 on spontaneous apoptosis of normal neutrophils. We considered the importance of the difference between in vitro and in vivo results and developed a new in vitro system consisting of a combination of immune cells and T helper (Th) cytokines. Extract of Dermatophagoides pteronyssinus (DP), S100A8, and S100A9 inhibited neutrophil apoptosis in culture of neutrophils alone without other leukocytes. DP and S100A8 more strongly suppressed neutrophil apoptosis in combinations of neutrophils, eosinophils, lymphocytes or monocytes than in a culture of neutrophils alone. Anti-apoptotic effect of S100A9 in the mixture of immune cells was similar to that in neutrophils. DP, S100A8, and S100A9 blocked neutrophil apoptosis, regardless of pretreatment with a T helper (Th) 1 cytokine (IFN-$\gamma$), Th2 cytokines (IL-4 and IL-10), a Th9 cytokine (IL-9), a Th17 cytokine (IL-17), a Treg-producing cytokine (TGF-$\beta$). These findings may enable elucidation of allergy pathogenesis due to HDM and DAMP.

Armeniacae Amarum Semen Contributes to the Chemotaxis of Eosinophils and Secretion of Chemokines in A549 Human Epithelial Cells (행인(杏仁)이 천식관련 chemokine 분비와 호산구 chemotaxis에 미치는 영향)

  • Jung, Hee-Jae;Jung, Sung-Ki;Rhee, Hyung-Koo;Ju, Chang-Yeop
    • The Journal of Internal Korean Medicine
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    • v.27 no.1
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    • pp.208-220
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    • 2006
  • Objective: Eosinophils are typically characterized by a bilobar nucleus with highly condensed chromatin and cytoplasm containing two major types of granules, specific and primary granules, and lipid bodies. The role of inflammation in asthma and other allergic diseases of the airways is widely appreciated, and airway inflammation is now included as a defining feature of asthma. The importance of the presence of eosinophils in the airways of patients with fetal asthma has long been recognized, but the mechanism by which these cells are recruited and retained in the lungs are only now being elucidated. Eotaxin is a potent and specific eosinophil chemoattractant that is mobilized in the respiratory epithelium after allergic stimulation. Methods : Water extracts of Armeniacae Amarum Semen(AAS) and pulmonary epithelial cell lines A549(alveolar typeII epithelial cells) and human eosinophils were used. Cytotoxic effects of AAS and MIS assay were estimated, as well as the effects of AAS on chemokines from prestimulated A549 cells by sandwich ELISA and RI-PCR. Chemotaxis assay was conducted on prestimulated eosinophils treated with AAS. Results : In this study it is demonstrated that $TGF-{\alpha}$, IL-4 and $IL-1{\beta}$ induced the accumulation of chemokine mRNAs in the alveolar epithelial cell lines A549 in dose-dependent manner. Eotaxin and IL-8 were inhibited by AAS in dose-dependent manner(p<0.05). Eosinophil migration was inhibited at high concentrations of AAS(p<0.05). Conculusions : These findings are indicative of suppression of eotaxin and IL-8, and suggest that this is accomplished through AAS treatment. This raises the possibility that AAS is of therapeutic value in diseases such as asthma.

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Effects of Gamisaenggan-tang on High Fat Diet-induced Nonalcoholic Fatty Liver Disease (가미생간탕(加味生肝湯)이 고지방식이로 유발된 지방간에 미치는 영향)

  • Choi, Mi-Young;Woo, Hong-Jung;Kim, Young-Chul;Lee, Jang-Hoon
    • The Journal of Internal Korean Medicine
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    • v.30 no.2
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    • pp.365-374
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    • 2009
  • Objectives : The aim of this study was to investigate the effects of Gamisaenggan-tang on high fat diet induced nonalcoholic fatty liver disease. Methods: Rats were randomly divided into four groups. The Normal group was fed a solid diet containing 10% fat. The Gamisaenggan-tang (GS) group was fed a solid diet containing 10% fat and Gamisaenggan-tang (90mg/100g body weight). The Control group was fed a solid diet containing 60% fat. The HFD-Gamisaenggan-tang (HFD-GS) group was fed a solid diet containing 60% fat and Gamisaenggan-tang (90mg/100g body weight). Six weeks later, rats body weight, liver weight, serum ALT, GGT, ALP levels were measured. Histological findings (Oil red O staining), hepatic triglyceride, TNF-${\alpha}$, and TGF-${\beta}$ levels in the liver tissue were studied. Results: Average body weight of the HFD-GS group was significantly less than that of the Control group. There were no significant liver weight differences among each group. The GGT levels of the HFD-GS group were significantly less than those of the Control group. However, there were no significant differences in the ALT or ALP levels among the groups. TNF-${\alpha}$ protein production assessed by western blot analysis was reduced by Gamisaenggan-tang. Greater fat accumulation was observed in the liver tissue of the Control group than in the HFD-GS group, which means the Gamisaenggan-tang has an inhibitory effect on the accumulation of fat in the liver. Conclusion : The results suggest that Gamisaenggan-tang can be potential candidate for the treatment of nonalcoholic fatty liver disease in clinics.

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The effects of Pulsed Ultrasound on the bone healing process in Fracture Model of Diabetes Mellitus Rat (당뇨병증 골절렛트의 골치유 과정에서 맥동성 초음파가 미치는 영향)

  • Min, Soon-Gyu;Chun, Jin-Sung;Yong, Jun-Hwan;Yoo, Young-Dae
    • The Journal of Korean Physical Therapy
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    • v.18 no.2
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    • pp.47-58
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    • 2006
  • Purpose: The study to pulsed ultrasound effects of diabetes mellitus fracture model in rat. Methods: We used 36 Sprague-Dawely rats which were divided into 3 groups; the animals were divided into group of 4 rats each 4th, 14th and 28th days. All animal was induced diabetes mellitus model to used streptozotocin with 45 mg/kg. Pulsed wave were divided into $50\;mW/cm^2$ and $100\;mW/cm^2$. Results: T-ALP value was significantly change from group II, III on 14th, 28th days (p<0.05). Especially T-ALP value to between groups was significantly change from group II on 14th days (p<0.05). Osteocalcin value was significantly change from group II on 28th days(p<0.05). At fracture site, osteoblast, osteoclast expression was observed from 4th days after treatment and it reached its maximum intensity at 28th days. At fracture site, $TGF-{\beta}_1$ expression was observed from 4th days after treatment and it reached maximum intensity at 14th days. Conclusion: According to this study, diabetes mellitus fracture model to the more effective is divided into $50m\;W/cm^2$ pulsed ultrasound.

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Effects of Samhwangsasim-tang on obesity-related metabolic disease in mice (삼황사심탕(三黃瀉心湯)이 수컷 생쥐의 비만(肥滿) 관련 대사질환(代謝疾患)에 미치는 영향)

  • Lee, Ju-Young;Kook, Yoon-Bum
    • Herbal Formula Science
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    • v.22 no.1
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    • pp.93-104
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    • 2014
  • Objectives : Samhwangsasim-tang (SHSST) is a traditional Korean medication, which has been used in Korea for treatment of hypertension and chest pain. Hyperlipidemia and inflammation could influence hypertension and chest pain. This study investigated whether and how SHSST reduces the hyperlipidemia and inflammation related to high-cholesterol diet-induced obesity in rats. Methods : Mice were divided randomly into four groups: the normal diet group, high-cholesterol diet group, low dose treatment group supplemented with 30% ethanol extract of SHSST (L) and high dose treatment group supplemented with 80% ethanol extract of SHSST (H). L and H groups were orally administered with SHSST at the dose of 50mg/kg a day respectively and others were administered with the same volume of physiological saline. Results : Administration of SHSST resulted in a decrease in serum levels of total cholesterol and low-density lipoprotein. Expression of hepatic genes(SREBP2, LXR, LDLR, and HMG-CoA) related with cholesterol metabolism was also suppressed. In addition, SHSST decreased the expression of inflammation-related gene (TNF-${\alpha}$, IL-6, ICAM-1, VCAM-1, TGF-${\beta}1$ and fibronectin). Histological examinations also showed that the size of the adipocytes was smaller in the SHSST treated group than in the high-colesterol diet group. In an in vitro study, SHSST inhibited the production of nitric oxide in a concentration-dependent manner. Conclusions : This study indicates that SHSST has anti-hyperlipidemia and anti-inflammatory effects. It may also suggest that SHSST may be alternative therapy for treatment of hyperlipidemia and its complications.

Ethanol Extract of Dioscorea batatas Stimulates Procollagen Production and Reduces UVB-induced MMPs Activity in Skin (마 에탄올추출물의 피부 collagen 합성 촉진 및 MMPs 활성 억제효과)

  • Kim, Dae Sung;Jeon, Byoung Kook;Lim, Nan Young;Mun, Yeun Ja;Lee, Young Eun;Woo, Won Hong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.27 no.2
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    • pp.183-188
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    • 2013
  • Ultraviolet (UV) B irradiation induces the production of matrix metalloproteinases (MMPs), which are responsible for the degradation or synthesis inhibition of collagenous extracellular matrix in connective tissues, causing skin photoaging. In this study, we examined the inhibitory effect of MMP-1 expression of yam extract in tumor necrosis factor-alpha (TNF-${\alpha}$)-stimulated human dermal fibroblast neonatal (HDFn) cell and preventive effect of UVB-induced damage in hairless mice skin. The synthesis of procollagen and the release of MMP-1 in HDFn cells were measured by EIA kit and MMP-1 assay kit, respectively. UVB radiation was applied to the backs of the mice three times a week for 8 weeks. Mice were randomly divided into three groups, and were topical application with the Dioscorea batatas (DB, 6%) or vehicle. Reduction of TNF-${\alpha}$-induced procollagen synthesis was increased by DB (50 ug/ml), which was higher than positive control group (TGF-${\beta}$). Also, pre-treatment of HDFn cells with DB inhibited TNF-${\alpha}$-induced release of MMP-1. In vivo study, we found that preventive effect of DB against UV-induced epidermal thickness. DB suppressed the expression of MMP-3 and MMP-13 induced by UVB irradiation. Our results show that DB have preventive effect of UV-induced skin damage in hairless mice.

Significance of Expression of Human METCAM/MUC18 in Nasopharyngeal Carcinomas and Metastatic Lesions

  • Lin, Jin-Ching;Chiang, Cheng-Feng;Wang, Shur-Wern;Wang, Wen-Yi;Kwan, Po-Cheung;Wu, Guang-Jer
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.1
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    • pp.245-252
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    • 2014
  • Human METCAM/MUC18, a cell adhesion molecule (CAM) in the immunoglobulin-like gene super family, plays a dual role in the progression of several epithelium cancers; however, its role in the nasopharyngeal carcinoma (NPC) remains unclear. To initiate the study we determined human METCAM/MUC18 expression in tissue samples of normal nasopharynx (NP), NPCs, and metastatic lesions, and in two established NPC cell lines. Immunoblotting analysis was used for the determination in lysates of frozen tissues, and immunohistochemistry (IHC) for expression in formalin-fixed, paraffin-embedded tissue sections of 7 normal nasopharynx specimens, 94 NPC tissue specimens, and 3 metastatic lesions. Human METCAM/MUC18 was expressed in 100% of the normal NP, not expressed in 73% of NPC specimens (or expressed at very low levels in only about 27% of NPC specimens), and expressed again in all of the metastatic lesions. The level of human METCAM/MUC18 expression in NPC tissues was about one fifth of that in the normal NP and metastatic lesions. The low level of human METCAM/MUC18 expression in NPC specimens was confirmed by a weak signal of RT-PCR amplification of the mRNA. Low expression levels of human METCAM/MUC18 in NPC tissues were also reflected in the seven established NPC cell lines. These findings provided the first evidence that diminished expression of human METCAM/MUC18 is an indicator for the emergence of NPC, but increased expression then occurs with metastatic progression, suggesting that huMETCAM/MUC18, perhaps similar to TGF-${\beta}$, may be a tumor suppressor, but a metastasis promoter for NPC.

Gene Microarray Assessment of Multiple Genes and Signal Pathways Involved in Androgen-dependent Prostate Cancer Becoming Androgen Independent

  • Liu, Jun-Bao;Dai, Chun-Mei;Su, Xiao-Yun;Cao, Lu;Qin, Rui;Kong, Qing-Bo
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9791-9795
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    • 2014
  • To study the gene expression change and possible signal pathway during androgen-dependent prostate cancer (ADPC) becoming androgen-independent prostate cancer (AIPC), an LNCaP cell model of AIPC was established using flutamide in combination with androgen-free environment inducement, and differential expression genes were screened by microarray. Then the biological process, molecular function and KEGG pathway of differential expression genes are analyzed by Molecule Annotation System (MAS). By comparison of 12,207 expression genes, 347 expression genes were acquired, of which 156 were up-ragulated and 191 down-regulated. After analyzing the biological process and molecule function of differential expression genes, these genes are found to play crucial roles in cell proliferation, differntiation, cell cycle control, protein metabolism and modification and other biological process, serve as signal molecules, enzymes, peptide hormones, cytokines, cytoskeletal proteins and adhesion molecules. The analysis of KEGG show that the relevant genes of AIPC transformation participate in glutathione metabolism, cell cycle, P53 signal pathway, cytochrome P450 metabolism, Hedgehog signal pathway, MAPK signal pathway, adipocytokines signal pathway, PPAR signal pathway, TGF-${\beta}$ signal pathway and JAK-STAT signal pathway. In conclusion, during the process of ADPC becoming AIPC, it is not only one specific gene or pathway, but multiple genes and pathways that change. The findings above lay the foundation for study of AIPC mechanism and development of AIPC targeting drugs.