• Title/Summary/Keyword: Phorbol 12-myristate 13-acetate

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Zanthoxylum Piperitum Attenuates the Allergic Inflammation in vivo and in vitro

  • Jeong, Duck-Ja;Kim, Su-Jin
    • Biomedical Science Letters
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    • v.26 no.3
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    • pp.192-200
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    • 2020
  • Natural products have received revived interest via traditional remedies or alternative medicine used for the treatment of various diseases. Zanthoxylum piperitum (ZP) has been utilized in traditional medicine for various medicinal purposes. The present study was conducted to evaluate whether ZP modulates allergic inflammation both in vivo and in vitro. We examined the pharmacological effects of ZP on 2, 4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) symptoms in mice. Additionally, in order to clarify the anti-inflammatory mechanisms of ZP, we elucidate the effect of ZP on the expression levels of inflammatory cytokines and nuclear factor-κB (NF-κB) in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1). The results demonstrated that ZP attenuated AD clinical symptoms such as erythema, edema and dryness as well as histamine and IgE serum levels in DNCB-induced AD model mice. Additionally, ZP suppressed the expression of inflammatory cytokines and activation of NF-κB in AD-like skin lesions and stimulated HMC-1. These results provide experimental evidence that ZP may be useful candidate for treating allergic inflammation including AD.

Inhibitory effects of lysozyme on endothelial protein C 1receptor shedding in vitro and in vivo

  • Ku, Sae-Kwang;Yoon, Eun-Kyung;Lee, Hyun Gyu;Han, Min-Su;Lee, Taeho;Bae, Jong-Sup
    • BMB Reports
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    • v.48 no.11
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    • pp.624-629
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    • 2015
  • Lysozyme protects us from the ever-present danger of bacterial infection and binds to bacterial lipopolysaccharide (LPS) with high affinity. Beyond its role in the activation of protein C, the endothelial cell protein C receptor (EPCR) plays an important role in the cytoprotective pathway. EPCR can be shed from the cell surface, which is mediated by tumor necrosis factor-α converting enzyme (TACE). However, little is known about the effects of lysozyme on EPCR shedding. We investigated this issue by monitoring the effects of lysozyme on phorbol-12-myristate 13-acetate (PMA)-, tumor necrosis factor (TNF)-α-, interleukin (IL)-1βand cecal ligation and puncture (CLP)-mediated EPCR shedding and underlying mechanism. Data demonstrate that lysozyme induced potent inhibition of PMA-, TNF-α-, IL-1β-, and CLP-induced EPCR shedding. Lysozyme also inhibited the expression and activity of PMA-induced TACE in endothelial cells. These results demonstrate the potential of lysozyme as an anti-EPCR shedding reagent against PMA-mediated and CLP-mediated EPCR shedding.

Rubus croceacanthus Leveille inhibits mast cell-mediated immediate-type allergic reactions and tumor necrosis factor-$\alpha$ secretion

  • Moon, Phil-Dong;Park, In-Young;Na, Ho-Jeong;Hong, Seung-Heon;Kim, Hyung-Min
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2003.11a
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    • pp.99-99
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    • 2003
  • We studied the effect of Rubus croceacanthus Leveille (RCL) on mast cell-mediated anaphylactic reactions. RCL inhibited compound 48/80-induced systemic anaphylactic shock. When RCL was given at concentrations ranging from 0.01 to 1 mg/$m\ell$, the histamine release from rat peritoneal mast cells induced by compound 48/80 was reduced in a dose-dependent manner. RCL also inhibited passive cutaneous anaphylaxis activated by anti-dinitrophenyl IgE. In addition, RCL inhibited phorbol 12-myristate 13-acetate and A23187-induced tumor necrosis factor-${\alpha}$ secretion from human mast cell line HMC-1 cells. These results indicate that RCL may possess a strong anti-anaphylactic activity.

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Redifferentiation of Dedifferentiated Chondrocytes on Chitosan Membranes and Involvement of PKCα and P38 MAP Kinase

  • Lee, Yoon Ae;Kang, Shin-Sung;Baek, Suk-Hwan;Jung, Jae-Chang;Jin, Eun Jung;Tak, Eun Nam;Sonn, Jong Kyung
    • Molecules and Cells
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    • v.24 no.1
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    • pp.9-15
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    • 2007
  • To investigate the effects of chitosan on the redifferentiation of dedifferentiated chondrocytes, we used chondrocytes obtained from a micromass culture system. Micromass cultures of chick wing bud mesenchymal cells yielded differentiated chondrocytes, but these dedifferentiated during serial monolayer subculture. When the dedifferentiated chondrocytes were cultured on chitosan membranes they regained the phenotype of differentiated chondrocytes. Expression of protein kinase $C{\alpha}$ ($PKC{\alpha}$) increased during chondrogenesis, decreased during dedifferentiation, and increased again during redifferentiation. Treatment of the cultures with phorbol 12-myristate 13-acetate (PMA) inhibited redifferentiation and down-regulated $PKC{\alpha}$. In addition, the expression of p38 mitogen-activated protein (MAP) kinase increased during redifferentiation, and its inhibition suppressed redifferentiation. These findings establish a culture system for producing chondrocytes, point to a new role of chitosan in the redifferentiation of dedifferentiated chondrocytes, and show that $PKC{\alpha}$ and p38 MAP kinase activities are required for chondrocyte redifferentiation in this model system.

Inhibitory Effects of Water Extract of Lindera obtusiloba on the Mast Cell-Mediated Allergic Inflammation (생강나무 추출물의 알레르기성 염증반응 억제 효과)

  • Kim, Sang-Hyun;Son, Jun-Ho;Lee, Seung-Ho
    • Korean Journal of Pharmacognosy
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    • v.40 no.3
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    • pp.233-237
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    • 2009
  • Lindera obtusiloba has been used for centuries as a traditional medicine in Korea and recently known to have an anti-fibrotic effect. In this report, we investigated the effect of hot water extract from L. obtusiloba (WELB) on the mast cell-mediated allergic inflammation and studied its possible mechanisms of action. WELB inhibited phorbol-12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-induced histamine release in HMC-1 human mast cells. WELB reduced PMACI-induced gene expression and secretion of proinflammatory cytokines such as tumor necrosis factor-$\alpha$, interleukin (IL)-$1{\beta}$, IL-6, and IL-8. The inhibitory effect of WELB on the expression of proinflammatory cytokines was c-jun N-terminal kinase and nuclear factor-${\kappa}B$ dependent. These results indicate that WELB may be beneficial in the treatment of mast cell-mediated allergic inflammation.

NO Formation of the PMA and LPS-activated Rat Kupffer- and Endothelial Cells in vitro (In Vitro에서 PMA와 LPS로 활성화된 흰쥐 간내 Kupffer-와 Endothelial 세포에서의 NO 형성에 관한 연구)

  • 김기성
    • Biomolecules & Therapeutics
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    • v.3 no.3
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    • pp.188-191
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    • 1995
  • The Present study was undertaken to indicate the major source of NO by liver cells in vitro. Even at early stages of induction or low LPS concentrations, NO was produced at high rates by LPS(Lipopolysaccharide) on the isolated rat kupffer cells. PMA(phorbol 12-myristate 13-acetate) induced NO formation at low rates in the same cells. IFN-${\gamma}$ (Interferon-${\gamma}$) alone had not induced NO formation but it stimulated the effects of LPS. Calcium ionophore A23187 caused no stimulatory effect. It suggests that LPS has especially strong NO inducer on the kupffer cells and its mechanism is related to those on macrophage in other organs. In other nonparenchymal liver cells, sinusoidal endothelial cells were not stimulated to produce NO either by inducers of aortic endothelium(A23187, ATP and ADP) or by effectors of macrophages(LPS, IFN-${\gamma}$. This results suggest that rat liver kupffer cells appear to be the major source of NO by liver cells in vitro. But in vivo, liver endothelial cells may still be capable of producing NO. Furthermore, kupffer cells may produce factors that facilitate NO production by the endothelial cells.

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Structural Features of Polyphenolic Compounds in Their NO Inhibitory Activities

  • Kim, Byung-Hun;Lee, Yong-Gyu;Kim, Tae-Woong;Cho, Jae-Youl
    • Biomolecules & Therapeutics
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    • v.17 no.1
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    • pp.79-85
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    • 2009
  • Polyphenolic compounds are reported to have various pharmacological activities such as anti-oxidative, anti-cancerous, anti-inflammatory and anti-aging effects. Although numerous papers explore their functional roles in many different cellular actions, not many studies handle their structural features in anti-inflammatory responses. In this study, therefore, we examined structural role of substituted transstilbenes in their NO inhibitory and NF-${\kappa}B$ suppressive activities. Of 10 compounds tested, 4 compounds (cinnamic acid, resveratrol, piceatannol and curcumin) displayed NO inhibitory activities in a dose-dependent manner. Similarly, these compounds blocked LPS-induced cytotoxicity of RAW264.7 cells. All NO inhibitory compounds also inhibited $I{\kappa}B{\alpha}$ phosphorylation, a hallmark for NF-${\kappa}B$ activation. However, these inhibitory compounds exhibited distinct suppressive pattern in tumor necrosis factor (TNF)-${\alpha}$- or phorbol-12-myristate-13-acetate (PMA)-induced NF-${\kappa}B$ and AP-1 activation. According to structure-activity relationship study, polarity and size of ring B seem to be important for diminishing NO production. Therefore, our data suggest that substituted trans-stilbenes can be developed as novel anti-inflammatory drug or further developed as lead compounds for another improvement.

Pyunkang-hwan (Pyunkang-tang) Regulates Hypersecretion of Pulmonary Mucin from Rats with Sulfur Dioxide-Induced Bronchitis and Production and Gene Expression of MUC5AC Mucin from Human Airway Epithelial Cells

  • Seo, Hyo-Seok;Lee, Hyun Jae;Lee, Choong Jae
    • Natural Product Sciences
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    • v.20 no.3
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    • pp.196-201
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    • 2014
  • Pyunkang-hwan (Pyunkang-tang) extract (PGT) is a traditional folk medicine for controlling diverse pulmonary diseases including bronchitis, tonsiltis and pneumonitis. We investigated whether PGT significantly affects secretion, production and gene expression of airway mucin using in vivo and in vitro experimental models reflecting the hypersecretion and/or hyperproduction of mucus observed in inflammatory pulmonary diseases. For in vivo experiment, effect of PGT was checked on hypersecretion of pulmonary mucin in sulfur dioxide-induced bronchitis in rats. For in vitro experiment, confluent NCI-H292 cells were pretreated with PGT for 30 min and then stimulated with EGF (epidermal growth factor), PMA (phorbol 12-myristate 13-acetate) or TNF-${\alpha}$ (tumor necrosis factor-${\alpha}$) for 24 h. The MUC5AC mucin gene expression and mucin protein production were measured by RT-PCR and ELISA. The results were as follows: (1) PGT inhibited the expression of MUC5AC mucin gene induced by EGF, PMA or TNF-${\alpha}$ from NCI-H292 cells, respectively; (2) PGT also inhibited the production of MUC5AC mucin protein induced by the same inducers from NCI-H292 cells, respectively; (3) PGT inhibited secretion of mucin in sulfur dioxide-induced bronchitis rat model. This result suggests that PGT can regulate secretion, production and gene expression of airway mucin.

The Extract of Gleditsiae Spina Inhibits Mast Cell-Mediated Allergic Reactions Through the Inhibition of Histamine Release and Inflammatory Cytokine Production

  • Shin, Tae-Yong
    • Natural Product Sciences
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    • v.16 no.3
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    • pp.185-191
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    • 2010
  • Mast cell-mediated allergic disease is involved in many diseases such as anaphylaxis, asthma and atopic dermatitis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. In the present study, the effect of water extract of Gleditsiae Spina (WGS) (Leguminosae), on compound 48/80-induced systemic allergic reaction, anti-DNP IgE antibody-induced local allergic reaction, and histamine release from human mast cell line (HMC-1) cells were studied. In addition, the effect of WGS on phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 (A23187)-induced gene expression and secretion of pro-inflammatory cytokines were investigated using HMC-1 cells. WGS was anally administered to mice for high and fast absorption. WGS inhibited compound 48/80-induced systemic allergic reaction. WGS dose-dependently decreased the IgE-mediated passive cutaneous anaphylaxis. WGS reduced histamine release from HMC-1 cells. In addition, WGS decreased the gene expression and secretion of pro-inflammatory cytokines in PMA plus A23187-stimulated HMC-1 cells. These findings provide evidence that WGS could be a candidate as an antiallergic agent.

Effect of Colostral Whey Fraction on the Proliferation of EL-4 Cell (초유 유청분획의 EL-4 세포 증식 효과)

  • Ha Woel-Kyu;Won Do-Hee;Yang Hee-Jin;Hwang Kyung-A;Lee Soo-Won
    • Food Science of Animal Resources
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    • v.25 no.2
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    • pp.244-249
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    • 2005
  • To investigate the effect of Holstein colostrum peptide fraction on proliferation of immune cell, polypeptide fractions were separated from acid whey into 3 fractions depending on molecular weight by ultrafiltration: Fraction I, which contains the polypeptide larger than 10,000 Da, Fraction n, which contains the polypeptide ranging from 1,000 Da to 10,000 Da and Fraction III, which contains the polypeptide smaller than 1,000 Da. EL-4 cell (murine T lymphoma cell) was used to evaluate immune enhancing effect of each fraction from Holstein colostrum. Fraction n showed the highest proliferative effect of the colostrum whey fractions on EL-4 cell at 1mg/mL compared with whole whey and other fractions and this proliferative activity was shown in dose dependent manner. Fraction n showed the highest proliferative effect on PMA (Phorbol 12-myristate 13-acetate) stimulated EL-4 cell. Heated Fraction n showed similar effect to native one on proliferation of both EL-4 cell and PMA stimulated EL-4 cell.