• 제목/요약/키워드: STAT1/STAT6

검색결과 177건 처리시간 0.022초

두시 하태독법이 시행된 비만 생쥐에서 Th2 분화조절을 통한 알러지성 비염 유발 감소 효과 (Effects of Douchi Hataedock Treatment on Induction of Allergic Rhinitis in Obese Induced NC/Nga Mice)

  • 안상현;김기봉
    • 대한한방소아과학회지
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    • 제32권2호
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    • pp.1-10
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    • 2018
  • Objectives This study investigated the effects of Hataedock treatment with Douchi on induction of allergic rhinitis in obese induced NC/Nga mice. Methods NC/Nga mice were divided into control group (Ctrl), allergic rhinitis induced obese mice group (ARE), and allergic rhinitis induced obese mice group with Douchi Hataedock treatment (FGT). The 3-week-old mice of the FGT group were given one 10 mg/kg dose of Douchi Hataedock extract and sensitized with allergic antigens at weeks 4, 5, and 6. After 1 week of final sensitization, allergic rhinitis was induced primarily in mice nasal cavities for five days. After one week of the completion with the first induction, the second induction was introduced by the same method. After 1 week, few samples of the nasal mucosal tissues of each group were prepared. The factor of Th2 differentiation and inflammation control such that IL-4, STAT6, CD40, $Fc{\varepsilon}RI$, substance P, MMP-9, $NF-{\kappa}B$ p65, p-IkB, iNOS and COX-2 were observed by immunohistochemistry. Also, the difference in nasal mucosal injury was observed by histochemical method (PAS staining). Results The FGT group showed that reduced IL-4 production, STAT6 expression and CD40 expression by regulating excessive Th2 differentiation. Also, production of substance P and MMP-9 and activity of $Fc{\varepsilon}RI$ in mast cells were decreased. Inhibition of $NF-{\kappa}B$ p65 activity was induced by inhibition of p-IkB, and the production of inflammatory enzymes iNOS and COX-2 were decreased. In addition, the damage of intramural respiratory epithelium was low and excessive mucin secretion in goblet cells was low. Conclusions This study confirmed the possibility of controlling the allergic rhinitis in obese children who are expected to have an overactive inflammation.

연교(連翹) 에탄올 추출물의 대식세포의 염증성 사이토카인 합성과 신호전달에 대한 조절 (Effect of Forsythiae Fructus ethanol extract on inflammatory cytokine production and cellular signaling pathways in mouse macrophages)

  • 남정범;이미화;최호영;손낙원;강희
    • 대한본초학회지
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    • 제27권1호
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    • pp.59-64
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    • 2012
  • Objective : This study was performed to evaluate the effect of Forsythiae Fructus (FF) ethanol extract on inflammatory cytokine production and its underlying mechanisms in mouse macrophages. Methods : Peritoneal macrophages from thioglycollate medium-injected mice were cultured and stimulated with lipopolysaccharide(LPS) or LPS/interferon(IFN)-${\gamma}$ for cytokine measurement and cellular signaling molecule analysis. Results : FF ethanol extract decreased the levels of secreted tumor necrosis factor(TNF)-${\alpha}$ and interleukin(IL)-6 in IFN-${\gamma}$/LPS-stimulated cells in a concentration-dependent manner. FF extract reduced IFN-${\gamma}$/LPS-induced STAT1 phosphorylation and LPS-induced p38 and JNK activation, but not ERK1/2 activity. The extract also inhibited LPS-induced $I{\kappa}B{\alpha}$ degradation through suppression of $I{\kappa}B{\alpha}$ kinase. Conclusions : These results suggest that FF ethanol extract affects the production of TNF-${\alpha}$ and IL-6 through inhibition of activation of STAT-1, $I{\kappa}B{\alpha}$, p38, and JNK.

Reversal of Cisplatin Resistance by Epigallocatechin Gallate Is Mediated by Downregulation of Axl and Tyro 3 Expression in Human Lung Cancer Cells

  • Kim, Kyung-Chan;Lee, ChuHee
    • The Korean Journal of Physiology and Pharmacology
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    • 제18권1호
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    • pp.61-66
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    • 2014
  • Lung cancer is still the number one cause of death from cancer worldwide. The clinical effect of platinum-based chemotherapy for non-small cell lung cancer is constrained by the resistance to drug. To overcome chemo-resistance, various modified treatment including combination therapy has been used, but overall survival has not been improved yet. In this study, chemo-resistant lung cancer cells, A549/Cis and H460/Cis, were developed by long-term exposure of cells to cisplatin and the proliferative capability of these resistant cells was verified to be reduced. We found cytotoxic effect of epigallocatechin gallate (EGCG), a major catechin derived from green tea, on both the parental lung cancer cells, A549 and H460, and their cisplatin resistant cells, A549/Cis and H460/Cis. ELISA and Western blot analysis revealed that EGCG was able to increase interlukine-6 (IL-6) production per cell, whereas its downstream effector Signal transducers and activators of transcription 3 (STAT3) phosphorylation was not changed by EGCG, indicating that IL-6/STAT3 axis is not the critical signaling to be inhibited by EGCG. We next found that EGCG suppresses the expression of both Axl and Tyro 3 receptor tyrosine kinases at mRNA and protein level, explaining the cytotoxic effect of EGCG on lung cancer cells, especially, regardless of cisplatin resistance. Taken together, these data suggest that EGCG impedes proliferation of lung cancer cells including their chemo-resistant variants through downregulation of Axl and Tyro 3 expression.

Anticancer Activity of Novel Daphnane Diterpenoids from Daphne genkwa through Cell-Cycle Arrest and Suppression of Akt/STAT/Src Signalings in Human Lung Cancer Cells

  • Jo, Si-Kyoung;Hong, Ji-Young;Park, Hyen Joo;Lee, Sang Kook
    • Biomolecules & Therapeutics
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    • 제20권6호
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    • pp.513-519
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    • 2012
  • Although the immense efforts have been made for cancer prevention, early diagnosis, and treatment, cancer morbidity and mortality has not been decreased during last forty years. Especially, lung cancer is top-ranked in cancer-associated human death. Therefore, effective strategy is strongly required for the management of lung cancer. In the present study, we found that novel daphnane diterpenoids, yuanhualine (YL), yuanhuahine (YH) and yuanhuagine (YG) isolated from the flower of Daphne genkwa (Thymelaeaceae), exhibited potent anti-proliferative activities against human lung A549 cells with the $IC_{50}$ values of 7.0, 15.2 and 24.7 nM, respectively. Flow cytometric analysis revealed that the daphnane diterpenoids induced cell-cycle arrest in the G0/G1 as well as G2/M phase in A549 cells. The cell-cycle arrests were well correlated with the expression of checkpoint proteins including the up-regulation of cyclin-dependent kinase inhibitor p21 and p53 and down-regulation of cyclin A, cyclin B1, cyclin E, cyclin dependent kinase 4, cdc2, phosphorylation of Rb and cMyc expression. In the analysis of signal transduction molecules, the daphnane diterpenoids suppressed the activation of Akt, STAT3 and Src in human lung cancer cells. The daphnane diterpenoids also exerted the potent anti-proliferative activity against anticancer-drug resistant cancer cells including gemcitabine-resistant A549, gefitinib-, erlotinib-resistant H292 cells. Synergistic effects in the growth inhibition were also observed when yuanhualine was combined with gemcitabine, gefitinib or erlotinib in A549 cells. Taken together, these findings suggest that the novel daphnane diterpenoids might provide lead candidates for the development of therapeutic agents for human lung cancers.

Persicaria senticosa Ameliorates Imiquimod-induced Psoriasis-like Skin Lesions in Mice via Suppression of IL-6/STAT3 Expression and Proliferation of Keratinocytes

  • Jung, Sangmi;Park, Jeong-Ran;Ra, Moonjin;Kim, Young Han;Yu, Ji Hoon;Lee, Yongjun
    • Natural Product Sciences
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    • 제26권2호
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    • pp.136-143
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    • 2020
  • Psoriasis is one of the most common inflammatory skin disorders, with a global prevalence of 2% - 3%. It is an autoimmune skin disorder characterized by excessive generation of plaques on the skin with typical long-lasting red, itchy, and scaly lesions. In this study, we aimed to elucidate the anti-psoriatic effect of the methanolic extract of Persicaria senticosa (PS), a bioactive edible plant extract used in traditional medicine, using a mouse model of imiquimod (IMQ)-induced psoriasis. The daily topical application of IMQ could induce human psoriasis-like lesion. The extract ameliorated IMQ-induced psoriasis. Furthermore, hematoxylin and eosin staining and the Psoriasis Area and Severity Index (PASI) scores indicated that topical application of PS led to an improvement in erythema, scaling, and thickness scores of the mouse dorsal skin and a considerable decrease in the epidermal thickness of the ear and dorsal skin in the IMQ-induced psoriatic mouse model. We also studied the effect of PS on the proliferation of keratinocytes using HaCaT cells. The extract inhibited cell proliferation and IL-6 and pSTAT3 expression induced by M5 cocktail (comprising interleukin [IL]-1α, IL-17A, IL-22, oncostatin M, and tumor necrosis factor-α) in HaCaT cells. Thus, PS might serve as a potential therapeutic agent for the treatment of psoriasis.

Induction of antiviral mechanisms by interferon-related genes in rock bream (Oplegnathus fasciatus) infected with rock bream iridovirus (RBIV)

  • Myung-Hwa Jung
    • 한국어병학회지
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    • 제36권2호
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    • pp.213-228
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    • 2023
  • We evaluated the transcriptional response of interferon (IFN)-related genes in rock bream iridovirus (RBIV)-infected rock bream under high-, low-, or no-mortality conditions induced by different stocking water temperatures. Under the high susceptibility condition (group A, water temperature 26℃, 100% mortality), only the Mx gene was expressed early, with prolonged expression, and with heavy viral loads of approximately 106~107 major capsid protein gene copies/μL from 4 to 10 days post infection (dpi). However, IRF1, IRF3, IRF8, STAT1, ISG15, PKR, Viperin, GVIN1, IFI44, and ISG56 were activated at later time points (8 dpi) and then quickly decreased (10 dpi). For the low susceptibility condition, the water temperature was set at 23℃ for 7 days (group B) and then reduced to 17℃. Group B exhibited a 28% mortality rate, in which persistent and effective antiviral responses were observed for long periods of time. In particular, at 20 and 22 dpi, when virus replication was peaked at approximately 107/μL, the expressions of most of the IFN-related genes (IRF1, IRF3, IRF8, Mx, STAT1, ISG15, PKR, Viperin, GVIN1, IFI44, and ISG56) were significantly higher in group B than in the control group. Moreover, prolonged and higher levels of IRF3 (at least 30 dpi), IRF8 (at least 30 dpi), ISG15 (at least 30 dpi), PKR (at least 28 dpi), Viperin (at least 30 dpi), and IFI44 (at least 30 dpi) were also observed in the recovery stage of infection. Under the no-susceptibility condition at 17℃ (0% mortality), significantly elevated levels of IRF3, Mx, ISG15, and PKR were observed mostly until 20 dpi. The findings indicate that RBIV infection can induce an efficient IFN-mediated antiviral immune response in low- and no-susceptibility conditions. The findings could be valuable for effective control of viral pathogens in fish.

소풍도적탕(消風導赤湯)이 아토피 피부염의 항염증효과와 각질층 ceramide변화에 미치는 영향 (Changes in Ceramide in Stratum Corneum and Anti-inflamatory Effects of Sopungdojeok-tang on Atopic Dermatitis)

  • 강윤호;김성아
    • 대한한방내과학회지
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    • 제27권1호
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    • pp.72-83
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    • 2006
  • Objective : This study was designed to identify lipid protection formation in stratum corneum and anti-inflammatory effects of Sopungdojeok-tang(SD) on atopic dermatitis(AD). Materials and Methods : In Vivo, SD extract was orally administered to BALB/c mice at $2.5m{\ell}/kg/day$ for 2 days after 5% sodium dodecyl sulfate evoked atopic dermatitis in abdominal skin. Morphological changes were observed by immunohistochemical stain using monoclonal antibodies(BrdU, ceramide, MIP-2, $NF-{\kappa}B$ p50, IL-4, and STAT6) and TUNEL method. In vitro, the alterations of IL-4 mRNA expression were detected by RT-PCT in SD extract treated EL4 cells after phorbol-12-myristate-13-acetate and 4-tert-Octylphenol induce Th2 skewed condition. Results : SD is used in Oriental Medicine for its potential curative for atopic dermatitis. In this study, we have investigated the anti-inflammatory and lipid lamella repair effects of SD were investigated. SD decreased the number of eosinophil in atopic dermatitis induced mice. In the histological properties, the hyperplasia, edema, infiltration of lymphocytes, damage of intercellular space of stratum corneum, BrdU positive reacted cells in stratum basal, and degranulated mast cells and capillaries in dermal papillae decreased in mice with SD. Treatment of SD also decreased MIP-2, STAT6 and IL-4 in dermal papillae. The IL-4 mRNA expression decreased in a dose-dependant manner in SD treated EL4 cells. In addition, decrease of $NF-{\kappa}B$ p50 and increase of apoptotic cells in dermis were observed in SD treated mice. These data suggest that SD may beneficial for atopic dermatitis. Conclusions : These data suggest that SD is beneficial in treatment of atopic dermatitis, and that SD provides lipid protection in stratum corneum and anti-inflammatory effects on atopic dermatitis.

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알콜증류폐액을 이용한 빵효모배양에서 포도당, 암모늄 및 인산의 자동첨가에 의한 증균 (Increasing Cell Concentration by the Automatic Addition of Glucose, Ammonium and Phosphate in the Cultivation of a Baker′s Yeast in Alcohol Distillery Wastewater)

  • 이형춘
    • KSBB Journal
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    • 제18권3호
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    • pp.197-201
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    • 2003
  • 알콜증류 폐액에 빵효모를 배양하는 중에 포도당, 암모늄 및 인산을 자동 첨가하여 균체량을 효율적으로 증가시킴으로써 폐액의 재이용성을 향상시키고자 하였다. 포도당은 DO를 제어파라미터로 하는 제어방법을 사용하여 자동 첨가함으로서 그 농도를 300 mg/L 이하로 유지하였다. 암모늄은 pH-stat 방법을 사용하여 N $H_4$OH로서 자동 첨가함으로서 12.6~17.4mM의 낮은 농도범위로 유지하였다. 인산의 경우에는 분석방법으로써 ascorbic acid법을 채택한 자동화 FIA sysetm을 제작하여 사용하였다. 이 system으로 배양 19.4 시간 후부터 배양액을 자동분석하고 제어한 결과 배양액의 P $O_4$-P 농도를 23.3~43.4 mg/L 의 낮은 농도범위로 유지할 수 있었다. 세가지 영양성분을 자동첨가하면서 배양한 결과 증식의 정체없이 균체량을 33.0배 더 증가시킬 수 있었다. 비증식속도는 0.19 $hr^{-l}$였다.

Streptozotocin으로 유발한 당뇨병성 쥐에서의 당뇨병성 백내장과 망막병증에 대한 구기자와 황기 혼합 추출물 등의 면역 조절 및 예방 효과 (Effects of Lycii fructus and Astragalus membranaceus Mixed Extracts on Immunomodulators and Prevention of Diabetic Cataract and Retinopathy in Streptozotocin-induced Diabetes Rat Model)

  • 전윤희;문준웅;권혁중;정용준;안치선;김해란;허선진;임병우
    • 한국약용작물학회지
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    • 제18권1호
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    • pp.15-21
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    • 2010
  • This study was conducted to investigate the effects of Lycii fructus and Astragalus membranaceus mixed extracts on immunomodulators and prevention in a streptozotocin-induced diabetes rat model. A total of 28 male rats were divided into four dietary groups and fed a commercial diet (A), commercial diet plus induced diabetes by a streptozotocin (STZ) injection (B), induced diabetes by STZ plus medicinal crop extracts(I&$H^{(R)}$) diet (C), and medicinal crop extracts (I&$H^{(R)}$) diet (D). Immunoblotting analyses revealed cytokine expression, and ELISA analyses revealed immunoglobulin E and nitric oxide production. As a results, the tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and inducible nitric oxide synthase (iNOS) as a inflammatory cytokine were decreased. Interleukin-6 (IL-6) and signal transducer and activation of transcription 3 (STAT3) cytokine related in diabetes expression through JAK/STAT3 pathway were also decreased. Furthermore, immunoglobulin E and nitric oxide production were decreased in the serum and lens, respectively. These results suggest that Lycii fructus and Astragalus membranaceus mixed extracts provide positive effects on immunomodulators and prevention in diabetes and eye disease complications.

비만 유발 생쥐에서 Th2분화조절을 통한 황련-감초 하태독법의 알레르기성 비염 발현 억제효과 (Effect of Hataedock Method with Coptidis Rhizoma and Glycyrrhiza Uralensis in Allergic Rhinitis-induced Obese Mice)

  • 안상현;정아람;김기봉
    • 대한한방소아과학회지
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    • 제33권2호
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    • pp.22-31
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    • 2019
  • Objective This study is to learn the effects of Hataedock method using Coptidis rhizoma and Glycyrrhiza uralensis mixed extract on inflammatory response in allergic rhinitis-induced obese NC/Nga mice. Materials and Methods The mice were fed with high fat-diet to be obese, and were divided into 3 groups as follows; allergic rhinitis-induced obese mice group with Hataedock method (CGT, n=10), no treatment group (Ctrl), allergic rhinitis elicited obese mice group (ARE). To induce allergic rhinitis, NC/Nga mice of 3 weeks age were sensitized on 7, 8 and 9 weeks by ovalbumin antigen in intraperitoneal space. After 7 days of final sensitization, allergic rhinitis was initially induced in mice through nasal cavities for 5 days. After 1-week, allergic rhinitis was induced again by the same method. Histological examination was used to identify distribution of IL-4, CD40, STAT6, $Fc{\varepsilon}RI$, substance P, MMP-9, NF-${\kappa}B$ p65, iNOS and COX-2. Results Hataedock method significantly reduced IL-4, STAT6 and CD40 response (p<0.05). In CGT, the inhibition of Th2 differentiation decreased inflammatory mediators such as $Fc{\varepsilon}RI$, substance P, MMP-9, NF-${\kappa}B$ p65, iNOS and COX-2 (all p<0.05). The immunological improvement led reduction of respiratory epithelial damage and mucin secretion in goblet cell. Conclusion The results of this study show that the Hataedock method suppresses the expression of allergic rhinitis by decreasing the inflammatory mediators through the regulation of Th2 differentiation even when the inflammation reaction is increased by obesity. Therefore, Hataedock may have potential preventive measure of allergic rhinitis accompanied by obese.