• Title/Summary/Keyword: Fc receptor activity

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Fc fusion to Glucagon-like peptide-1 inhibits degradation by human DPP-IV, increasing its half-life in serum and inducing a potent activity for human GLP-1 receptor activation

  • Kim, Dong-Myung;Chu, Seoung-Ho;Kim, Se-Mi;Park, Young-Woo;Kim, Sung-Seob
    • BMB Reports
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    • v.42 no.4
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    • pp.212-216
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    • 2009
  • The short in vivo half-life of GLP-1 prevents it from being used clinically. This short half-life occurs because GLP-1 is rapidly degraded by dipeptidyl peptidases such as DPP-IV. To overcome this obstacle, a GLP-1/Fc was constructed and evaluated to determine if it was degraded by DPP-IV and in serum. When the degradation of GLP-1/Fc by human DPP-IV and rabbit serum was compared with that of GLP-1 it was found to be reduced by approximately 5- and 4-fold, respectively. Furthermore, GLP-1/Fc showed a potent activity for human GLP-1 receptor activation ($EC_{50}$ approximately 6 nM). Taken together, these results indicate that GLP-1/Fc may have an extended half-life in vivo that occurs as a result of inhibition of degradation by human DPP-IV. Due to the extended half life, GLP-1/Fc may be useful for clinical treatments.

Studies on the Activities of Peritoneal Macrophages Induced by Yookmijihwangtang, Palmijihwangtang and Gamijihwangtang (육미지황탕(六味地黃湯), 팔미지황탕(八味地黃湯) 및 가미지황탕(加味地黃湯)이 생쥐의 복강대식세포(腹腔大食細胞) 활성(活性)에 미치는 영향(影響))

  • Hahn, Il-Soo;Kim, Cheol-Joong
    • Journal of Haehwa Medicine
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    • v.6 no.1
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    • pp.331-347
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    • 1997
  • In order to investigate the effects of YOOKMIJIHWANGTANG, GAMIJIHWANGTANG and PALMIJIHWANGTANG on the various immune responses, the chemotactic, adherent, nitric oxide release ability of macrophages were studied in vivo and in vitro. The results obtained were follows : 1. The total number of peritoneal exudate cells from mice injected with three drugs were 2~3 times more than those from the PBS. 2. The administration of three drugs enhanced significantly the Fc receptor mediated activity(phagocytosis, rosette formation activity). 3. The administration of three drugs enhanced significantly the chemotactic activity of peritoneal macrophages. 4. The administration of three drugs enhanced significantly the adherent activity of macrophages and neutrophils. 5. The administration of GAMIJIHWANGTANG and PALMIJIHWANGTANG enhanced significantly the chemotatic activity of macrophages (p<0.01). And also the administration of YOOKMIJIHWANGTANG enhanced significantly the chemotatic activity of macrophages(p<0.05). 6. The administration of GAMIJIHWANGTANG and enhanced significantly the chemotatic activity of neutrophils(p<0.01). And also the administration of YOOKMIJIHWANGTANG and PALMIJIHWANGTANG enhanced significantly the chemotatic activity of neutrophils(p<0.05). From above findings, it is suggested that YOOKMIJDTWANGTANG, GAMIJIHWANGTANG and PALMIJIHWANGTANG seems to produce the increase of immune response such as the Fc receptor activity, chemotactic activity, adherent activity, nitrate release of macrophages. From the above results, the GAMIJIHWANGTANG among three drugs may be the most useful drug having immunostimulating effects.

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Inhibitory Effects of Chrysanthemum zawadsaki Ethanolic Extract on $Fc{\varepsilon}RI$ ${\alpha}$ Chain Expression (구절초 에탄올 추출물의 $Fc{\varepsilon}RI$ ${\alpha}$ chain 발현 저해효과)

  • Shim, Sun-Yup;Byun, Dae-Seok
    • Korean Journal of Food Science and Technology
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    • v.43 no.2
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    • pp.220-223
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    • 2011
  • Human basophilic KU812F cells express a high affinity for IgE receptor, $Fc{\varepsilon}RI$, which plays an important role in immunoglobulin E (IgE)-mediated allergic reactions. Using the human basophilic KU812F cells, we assessed the inhibitory effects of the ethanolic extract from Chrysanthemum zawadsaki(CZ) on $Fc{\varepsilon}RI$ ${\alpha}$ chain expression. Flow cytometric analysis showed that cell surface $Fc{\varepsilon}RI$ ${\alpha}$ chain expression was suppressed when the cells were cultured with CZ extract. RT-PCR analysis showed that the mRNAs for $Fc{\varepsilon}RI$ ${\alpha}$ chain decreased by the treatment of CZ extract. Moreover, CZ extract was also observed to result in a reduction in the release of histamine from anti-$Fc{\varepsilon}RI$ antibody (CRA-1)-stimulated cells. These results suggest that CZ extract may exert anti-allergic activity through down-regulation of $Fc{\varepsilon}RI$ ${\alpha}$ chain expression and a subsequent decrease in histamine release.

Inhibitory Effects of Paeonia suffruticosa Andrews Extracts on VEGF Binding to VEGF Receptor

  • Lee, Hak-Kyo;Lee, Sung-Jin
    • Natural Product Sciences
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    • v.13 no.2
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    • pp.128-131
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    • 2007
  • Tumor angiogenesis is a critical step f3r the growth and metastasis of solid tumors. Vascular endothelial growth factor (VEGF) is the most important angiogenic molecule associated with tumor-induced neovascularization. VEGF exerts its activity through binding to its receptor tyrosine kinase, KDR/Flk-1, expressed on the surface of endothelial cells. This study was carried out to investigate inhibitory effect of extracts from root cortex of Paeonia suffruticosa Andrews on VEGF binding to VEGF receptor. The MeOH extract from P. suffrutiocosa Andr. inhibited the binding of KDR/Flk-1-Fc to immobilized VEGF$_{165}$ more than 45% at the concentration of 100 ${\mu}$g/mL. The MeOH extract was further fractionated into n-hexane, ethyl acetate, n-BuOH, and aqueous fractions. Among the four fractions, the ethyl acetate fraction from the root cortex of P. suffruticosa Andr. exhibited highly effective inhibition (${\approx}$ 79% inhibition) and then n-BuOH fraction (${\approx}$ 45% inhibition) on the binding of KDR/Flk-1-Fc to immobilized VEGF$_{165}$ at the concentration of 100 ${\mu}$g/mL. The ethyl acetate fraction from the root cortex of P. suffruticosa Andr. more efficiently blocked VEGF-induced human umbilical vein endothelial cell proliferation, than the growth of HT1080 human fibrosarcoma. Our results suggest that P. suffruticosa Andr. may be used as a candidate fur developing anti-angiogenic agent.

Anti-inflammatory Effect of Sabaek-san Extract through ECS Control in Atopic Dermatitis (아토피피부염에서 ECS 조절을 통한 사백산추출물의 염증 완화 효과)

  • Ahn, Sang Hyun;Jeong, A Ram;Kim, Ki Bong
    • The Journal of Pediatrics of Korean Medicine
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    • v.36 no.3
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    • pp.87-96
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    • 2022
  • Objective The purpose of this study was to confirm the effect of Sabaek-san extract on skin damage recovery and inflammation relief in atopic dermatitis-induced mice through Endocannabinoid system (ECS) control. Methods In this study, we used 6-week-old NC/Nga mice were divided into 4 group: control group (Ctrl), lipid barrier elimination group (LBEG), palmitoylethanolamide (PEA) treated group after lipid barrier elimination (PEAG), and Sabaek-san extract treatment group after lipid barrier elimination (SBSG). Each group was assigned 10 animals. After drug administration of three weeks duration following lipid barrier elimination, cannabinoid receptor (CB) 1, CB2, CD (Cluster of Differentiation) 68, phosphorylated inhibitor kappa B (p-IκB), inducible nitric oxide synthase (iNOS), Fc ε receptor, substance P and serotonin were observed to confirm the regulation of the ECS, macrophage activity and mast cell activity. Results We found that 8-hydroxydeoxyguanosine (8-OXdG) positive reaction was significantly lower in the SBST group than in LBET and PEAT groups. Both CB1 and CB2 showed higher positive reactions in the SBST group than in the LBET and PEAT. CD68, p-IκB, iNOS, Fc ε receptor, Substance P and serotonin showed lower positive reaction in the SBST compared to the LBET and PEAT. Conclusion It was confirmed that the Sabaek-san extract can reduce the inflammation of atopic dermatitis by restoring the structural damage of the skin lipid barrier through ECS activity.

Studies on the prevention of tuberculosis in pet dogs 1. The effects of BCG pretreatment in pet dogs inoculated experimentally with Mycobacterium bovis (애완견의 결핵예방에 관한 연구 1. Mycobacterium bovis를 실험적으로 접종한 애완견에 있어서 BCG의 전처치 효과)

  • Kang, Jong-koo;Kim, Chang-ki
    • Korean Journal of Veterinary Research
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    • v.32 no.1
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    • pp.117-125
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    • 1992
  • Dogs were divided into 3 groups of two each; Bacillie Calmette-Guerin(BCG) pretreatment, M bovis only treatment and uninfected control group. BCG were vaccinated intradermally with 0.2ml before 3weeks of M bovis intraperitoneal infection. Infection at necropsy 4months later was readily in the both treated dogs. Histopathologically, the BCG pretreated dogs produce the moderate accumulation of macrophages and focal granuloma formation in the lung, whereas the M bovis only treared dogs produce the accumulation of predominantly macrophages, occasionaly polymorphonuclear cells and the more larger granuloma Bronchoalveolar lavage(BAL) was obtained and total and differential cell counts were examined. Total number of BAL cells harvested from uninfected dogs is lower compared with those of the both treated groups. The total cell number of M bovis only treated dogs were singificantly higher 1.8 times than that of the BCG pretreated dogs. The Fe receptor activity and the growth of organism in alveolar macrophages obtained from BCG pretreated dogs were compared with that in macrophages from M bovis only treated dogs. BCG vaccination resulted in substantial macrophage activation, measured as increased Fc receptor mediated phagocytosis and rosette formation, as wells as the inhibition of intracellular mycobacteria multiplication. However, actibated macrophages taken from BCG pretreated dogs are incapable of killing the M bovis. Thus, these results suggest that BCG pretrearment in the dog may produce a protective effect against tuberculosis because active alveolar macrophages have acquired antituberculous immunity, although few mycobacteria within the lung remain in a metabolically active state.

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Sanguiin H-6 Blocks Endothelial Cell Growth through Inhibition of VEGF Binding to VEGF Receptor

  • Lee Sung-Jin;Lee Hak-Kyo
    • Archives of Pharmacal Research
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    • v.28 no.11
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    • pp.1270-1274
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    • 2005
  • The vascular endothelial growth factor (VEGF) plays a key role in angiogenesis, which is a process where new blood vessels develop from the endothelium of a pre-existing vasculature. VEGF exerts its activity by binding to its receptor tyrosine kinase, KDR/Flk-1, which is expressed on the surface of endothelial cells. A methanol extract and organic solvent (n-hexane, ethyl acetate, n-butanol, aqueous) fractions from Rubus coreanus were examined for their inhibitory effects on VEGF binding to the VEGF receptor. The methanol extract from the crude drug were found to significantly inhibit VEGF binding to the VEGF receptor ($IC_{50}$$\thickapprox$27 $\mu$g/mL). Among the fractions examined, the aqueous fraction from the medicinal plant showed potent inhibitory effects against the binding of KDR/Flk-1-Fc to immobilized $VEGF_{165}$ in a dose­dependent manner ($IC_{50}$$\thickapprox$11 $\mu$g/mL). Sanguiin H-6 was isolated as an active principle from the aqueous fraction, and inhibited the binding of KDR/Flk-1-Fc to immobilized $VEGF_{165}$ in a dose­dependent manner ($IC_{50}$$\thickapprox$0.3 $\mu$g/mL). In addition, sanguiin H-6 efficiently blocked the VEGF­induced HUVEC proliferation in a dose-dependent manner ($IC_{50}$$\thickapprox$7.4 $\mu$g/mL) but had no effect on the growth of HT1080 human fibrosarcoma cells. This suggests that sanguiin H-6 might be a potential anti-angiogenic agent.

ECS Modulating Effect of Scutellaria baicalensis Extract on inflammation relief in atopic dermatitis-induced mice (황금 (Scutellaria baicalensis) 추출물의 ECS조절을 통한 아토피피부염 염증 완화 효과)

  • Ahn, Sang Hyun;Kim, Ki Bong
    • The Journal of Pediatrics of Korean Medicine
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    • v.35 no.3
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    • pp.118-127
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    • 2021
  • Objective The purpose of this study was to confirm the effect of Scutellaria baicalensis extract on skin damage recovery and inflammation relief in atopic dermatitis-induced mice through Endocannabinoid system (ECS) control. Methods 6-week-old Balb/C mice were divided into control group (Ctrl), atopic dermatitis induced group (ADE), palmitoylethanolamide (PEA) administered group after atopic dermatitis induced (PEAT), and Scutellaria baicalensis extract administered group after atopic dermatitis induced (SBT). Seven animals were assigned for each group. After drug administration for 3 weeks after inducing atopic dermatitis, Claudin and 8-OHdG were observed to confirm the recovery of the skin damage in each group. To confirm ECS regulation, CB1, CB2, and GPR55 were observed. To confirm the anti-inflammatory effect, Fc ε receptor, and MMP-9 was observed. Results Claudin positive reaction was significantly increased in SBT compared to ADE and PEAT. 8-OHdG positive reaction was significantly decreased in SBT compared to ADE and PEAT. CB1, CB2, and GPR55 positive responses were significantly increased in SBT compared to ADE and PEAT. Fc ε receptor and MMP-9 positivity were significantly decreased in SBT compared to ADE and PEAT. Conclusion It was confirmed that the Scutellaria baicalensis extract can reduce the inflammation of atopic dermatitis by restoring the structural damage of the skin lipid barrier through ECS activity.

Studies on the effects of Sojeokbaekchoolsan on the bleomycin induced pulmonary fibrosis and the antitumor activity (소적백출산(消積白朮散)이 Bleomycin의 부작용감소(副作用減少)와 항암효과(抗癌效果)에 미치는 영향(影響))

  • Kim, Tae-Woon;Son, Chang-Kyu;Cho, Chong-Kwan
    • THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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    • v.5 no.1
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    • pp.77-101
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    • 1999
  • l. Sojeokbaekchoolsan compound treatment decreased pulmonary fibrosis induced by Bleomycin. 2. At 1 and 2 days after bleomycin treatment, Sojeokbaekchoolsan compound treatment decreased the number of neutrophils in bronchoalveolar lavage than those of bleomycin alone treatment. 3. Sojeokbaekcoolsan compound treatment increased the Fc receptor mediated rosette activity of alveolar macrophage decreased by bleomycin treatment. 4, At 10 days after bleomycin treatment, Sojeokbaekchoolsan compound treatment decreased the lipid peroxidation of lung tissue than those of bleomycin alone treatment. 5. Anti-tumor activity of Sojeokbaekchoolsan and bleomycin compound group was higher than those of bleomycin alone treated group to ascitic tumor caused by Sarcoma-180 tumor cells.

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The Effect of Douchi Hataedock Treatment for Dermatophagoides Farinae-Induced Atopic Dermatitis-like Skin Lesions by Controlling IL-4 Activity (두시 하태독법의 IL-4 활성 조절이 D. farinae 유도 아토피유사피부염 발병 조절에 미치는 효과)

  • Ahn, Sang Hyun;Kim, Jae Kyu;Cheon, Jin Hong;Kim, Ki Bong
    • The Journal of Pediatrics of Korean Medicine
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    • v.31 no.1
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    • pp.43-51
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    • 2017
  • Objectives Hataedock method is a Korean medical therapy which removes fetal toxin by orally administering herbal decoction to neonates. This study was to observe skin damage and anti-inflammatory effect via regulating IL-4 activity in NC/Nga mice which were induced atopic dermatitis (AD)-like skin lesion by Dermatophagoides (D.) farinae after applying Douchi Hataedock method. Methods NC/Nga mice with 3 weeks of gestational age were used. Each 10 mice were allocated to the control group (Ctrl), the AD-induced group (AE), and the group which induced AD after administering Douchi extract (GT). After 4 weeks from administering Douchi extract to the mice, the primary AD was induced by applying D. farinae extract 6 times per week for 3 weeks and then the secondary AD was induced by the same method after 1 week from the primary AD induction. To identify the skin damage and anti-inflammatory effect, we observed LxR, IL-4, Fc ${\varepsilon}$ receptor, substance P, and $NF-{\kappa}B$. Results The GT group showed alleviation of skin injury and decrease in capillary angiogenesis. Stratum corneum damage, epithelial cell hyperplasia, lymphocyte infiltration, and capillary distribution relatively decreased in the GT group. LxR-positive reaction in the GT group were increased by 53% than that of the AE group. IL-4 production, $Fc{\varepsilon}$ receptor activity, and substance P-positive reaction in the GT group were decreased by 82%, 42%, and 82% respectively compare to those of the AE group. $NF-{\kappa}B$-positive reaction in the GT group were decreased by 15% compare to that of the AE group. Conclusions Hataedock method with Douchi extract alleviated AD via reducing inflammatory cytokines secreted at the early stage of AD. Thus, Douchi Hataedock method has a beneficial effect for the prevention and treatment of AD.