• Title/Summary/Keyword: pPMA

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Typha orientalis inhibits inflammatory cytokine expression through suppression of ERK phosphorylation in HMC-1 cells

  • Choi, In-Young;Na, Ho-Jeong;Um, Jae-Young;Kim, Hyung-Min;Hong, Seung-Heon;Sim, Kuk-Jin;Song, Bong-Keun;Nam, Gi-Hye;Choung, Se-Young;Jeong, Hyun-Ja
    • Advances in Traditional Medicine
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    • v.10 no.1
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    • pp.7-12
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    • 2010
  • Typha orientalis' stem (TOS) is traditionally used as an herbal medicine for difficulty in urination, galactophoritis purulenta, whooping cough, and allergic dermatitis. However, its effect in experimental models remains unknown. Here, we report the effect of TOS on the phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-induced inflammatory cytokine production and extracellular signal-regulated kinase (ERK) activation in the human mast cell line, HMC-1. TOS inhibited PMA plus A23187-induced cytokines such as tumor necrosis factor-alpha (TNF-$\alpha$) and interleukin (IL)-6. Maximal inhibition rate of TNF-$\alpha$ and IL-6 production by TOS (1 mg/ml) was about 44.02%, and 45.20%, respectively (P < 0.05). In addition, TOS inhibited the expression of TNF-$\alpha$ and IL-6 mRNA under the same condition. Moreover, TOS partially blocked PMA plus A23187-induced ERK phosphorylation. These results suggested TOS could inhibit the cytokine production through blocking of ERK activity.

PKC Downstream of PI3-Kinase Regulates Peroxynitrite Formation for Nrf2-Mediated GSTA2 Induction

  • Kim, Sang-Geon;Kim, Sun-Ok
    • Archives of Pharmacal Research
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    • v.27 no.7
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    • pp.757-762
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    • 2004
  • The protective adaptive response to electrophiles and reactive oxygen species is mediated by the induction of phase II detoxifying genes including glutathione S-transferases (GSTs). NF-E2-related factor-2 (Nrf2) phosphorylation by protein kinase C (PKC) is a critical event for its nuclear translocation in response to oxidative stress. Previously, we have shown that peroxynitrite plays a role in activation of Nrf2 and Nrf2 binding to the antioxidant response element (ARE) via the pathway of phosphatidylinositol 3-kinase (PI3-kinase) and that nitric oxide synthase in hepatocytes is required for GSTA2 induction. In view of the importance of PKC and Pl3-kinase in Nrf2-mediated GST induction, we investigated the role of these kinases in peroxynitrite formation for GSTA2 induction by oxidative stress and determined the relationship between PKC and PI3-kinase. Although PKC activation by phorbol 12-myristate-13-acetate (PMA) did not increase the extents of constitutive and inducible GSTA2 expression, either PKC depletion by PMA or PKC inhibition by staurosporine significantly inhibited GSTA2 induction by tert-butylhydroquinone (t-SHa) a prooxidant chemical. Therefore, the basal PKC activity is req- uisite for GSTA2 induction. 3-Morpholinosydnonimine (SIN-1), which decomposes and yields peroxynitrite, induced GSTA2, which was not inhibited by PKC depletion, but slightly enhanced by PKC activation, suggesting that PKC promotes peroxynitrite formation for Nrf2-mediated GSTA2 induction. Treatment of cells with S-nitroso-N-acetyl-penicillamine (SNAP), an exogenous NO donor, in combination with t-BHQ may produce peroxynitrite. GSTA2 induction by SNAP + t-BHQ was not decreased by PKC depletion, but rather enhanced by PKC activation, showing that the activity of PKC might be required for peroxynitrite formation. LY294002 a P13-kinase inhibitor blocked GSTA2 induction by t-BHQ, which was reversed by PMA-induced PKC activation. These results provide evidence that PKC may playa role in formation of peroxynitrite that activates Nrf2 for GSTA2 induction and that PKC may serve an activator for GSTA2 induction downstream of PI3-kinase.

Priming Effect of Endotoxin in Human Alveolar Macrophage (사람 폐포대식세포에서 내독소의 Priming 효과)

  • Chung, Man-Pyo;Yoo, Chul-Gyu;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo;Han, Yong-Chol
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.1
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    • pp.46-53
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    • 1996
  • Background: Endotoxin or lipopolysaccharide(LPS) can prime phagocytic cells such as polymorphonuclear leukocytes, monocytes or animal peritoneal macrophages to generate increased amounts of secretory products such as oxygen free radicals and tumor necrosis factor, which play an important role in developing adult respiratory distress syndrome in gram negative sepsis. Human alveolar macrophages(HAM) are continuously exposed to various stimuli inhaled into the alveoli, and the response to LPS might be different in HAM. Therefore, we investigated the effect of LPS pre-exposure on HAM adhered to plastic surface and A549 cell(type II human alveolar epithelial cell line) monolayer. Methods: HAM were isolated from bronchoalveolar lavage fluid from normal lung of the patients with localized lung cancer and esophageal cancer. LPS was exposed to HAM for 2hrs before or after adherence to plastic surface of 24-well Linbro plate and A549 cell monolayer. And then HAM was stimulated with PMA(phorbol myristate acetate) or fMLP(N-formyl-methionylleucyl-phenylalanine). The amount of hydrogen peroxide($H_2O_2$) production in the supernatant was measured on the principle of peroxidase-dependent oxidation of phenol red by hydrogen peroxide. Results: LPS pre-exposure could not enhance $H_2O_2$ production in neither HAM adhered to plastic surface nor one to A549 cell monolayer. But LPS even in the absence of PMA or fMLP stimulation directly increased $H_2O_2$ release in HAM if added after the adherence to A549 cell monolayer. Conclusion: Endotoxin does not prime HAM, but may directly activate HAM adhered to alveolar epithelial cells. Further investagation will be necessary.

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Regulatory Effect of Inflammatory Cytokines Secretion and Hypoxia-inducible $Factor-1{\alpha}$ Activation by Panax ginseng (인삼의 염증성 사이토카인 분비 및 저산소 유도인자-1${\alpha}$ 활성화 조절 효과)

  • Zo, Chul-Won;Lee, Seung-Hee;Kim, Dong-Woung;Lee, Seong-Kyun;Song, Bong-Keun
    • The Journal of Internal Korean Medicine
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    • v.27 no.4
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    • pp.864-878
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    • 2006
  • Purpose : Panax ginseng(PG) is considered to have salutary effects and stimulant actions on physical capacity. However, the effects of PG on the inflammatory cytokine secretion and hypoxia condition are still not understood. This study wasto elucidate the effect of PG on inflammatory cytokine secretion such as interleukin (IL)-1, IL-6, granulocyte macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor $(TNF)-{\alpha}$. Also, the effects on the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1) were measured. Methods : The water extract of PG was administrated to HMC-1 cells before phorbol myristate acetate (PMA)+A23187 treatment. $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, GM-CSF, and VEGF secretion were measured by a modified enzyme-linked immunosorbent assay (ELISA). HIF-1 activation was measured by transcription factor enzyme-linked immunoassay (TF-EIA) Results : PG significantly decreased secretion of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, and GM-CSF in PMA+A23187-induced HMC-1 cells. VEGF secretion was not changed but HIF-1 activation was decreased by the treatment of PG. Conclusions : PG inhibited the secretion of inflammatory cytokines, which impliesPG might contribute to treatment of mast cell-mediated inflammatory disease. Also, PG inhibited PMA+A23187-induced $HIF -1{\alpha}activation}$ and DNA-binding activity for HIF-1. Therefore, these data demonstrate that PG modulates inflammatory cytokines through inhibition of $HIF-1{\alpha}activation}$ activation.

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Electromyographic comparison of modified push-up exercise: focused on various arm position

  • Kim, You-Sin;Yang, Jae-Young;Lee, Nam-Ju
    • Journal of the Korean Applied Science and Technology
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    • v.35 no.1
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    • pp.36-42
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    • 2018
  • This study was to investigate the difference of muscle activities in trunk, upper arm, and shoulder during push-up exercise based on 3 types of different arm position(posterior position, PP; normal position, NP; and anterior position, AP) and to provide effective push-up arm position for each muscle development. Fifteen healthy males(age, $21.5{\pm}0.5years$; height, $172.7{\pm}1.0cm$; body mass, $70.5{\pm}1.3kg$; shoulder width, $42.3{\pm}0.6cm$; and BMI, $23.6{\pm}0.5kg/m^2$) participated in this study. PP, NP, and AP of the arm were used to conduct push-up exercise and 8 muscles(deltoideus p. acromialis: DA; pectoralis minor: PMI; pectoralis major: PMA; serratus anterior: SA; biceps brachii: BB; triceps brachii: TB; latissimus dorsi: LD; and infraspinatus: IS) of right side were selected to measure muscle activities. Total 9 counts of push-up exercise were conducted and EMG data signals of 5-time(from $3^{th}$ to $7^{th}$) push-up movement were used for measuring muscle activities. PP push-up exercise showed that there was a significantly higher muscle activity of DA, PMI, PMA, SA, BB, LD, and IS(p<.05) and AP push-up exercise showed a significantly higher TB activity(p<.05). It would be suggested that different arm position evokes various muscle activities when conducting push-up exercise. PP would be the best push-up arm position for inducing various trunk, upper arm, and shoulder muscle activities compared to NP and AP.

Effects of Substance P on the Cell Proliferation and IL-2 Production of T Lymphocyte (Substance P가 T 임파구의 세포증식과 IL-2 생산에 미치는 영향)

  • Moon, Jin-Kyun;Choi, Byung-Son;Lee, Seok-Cho;Kim, Hyung-Seop
    • Journal of Periodontal and Implant Science
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    • v.27 no.4
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    • pp.805-818
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    • 1997
  • Immune responses of periodontal tissue may be regulated by products of sensory afferent nerve endings such as neuropeptides. Substance P(SP), a tachykinin neuropeptide, has been previously reported to stimulate the activities of T lymphocyte. Therefore, I examined the role of SP in IL-2 production and cell proliferation by using a homogeneous line of T lymphocytes(Jurkat and HuT78). Cell proliferation rate was determined by [$^3H$]-thymidine incorporation test, and IL-2 was quantitated by the growth rate of CD4+ IL-2-dependent T lymphocyte line CTLL-2. SP stimulated cell proliferation of T lymphocytes at the concentration of $10^{-12}$ and $10^{-8}$M in a biphasic bell-shape dose-dependent manner. However, SP alone did not induce IL-2 release at the concentration range of $10^{-6}$ to $10^{-14}$M. The upregulation of IL-2 release was observed when $10^{-12}$M SP was applied together with mitogens such as Con A or PHA+PMA on T cell lines, especially on Jurkat. Con A or PHA+PMA demonstrated to increase the rate of cell proliferation of Jurkat, which had shown to produce much amount of IL-2 indicating that mitogen-induced cell proliferation might be partially influenced by released IL-2. It was concluded that regulatory effects of SP on the immune/inflammatory response could be mediated through the costimulatory upregulation of IL-2 production and increase of cell proliferation of T lymphocyte.

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Suppressive effects of Morus alba Linne Root Bark (MRAL) on activation of MC/9 mast cells (상백피에 의한 MC/9 비만세포의 활성 억제 조절 연구)

  • Lee, Ki Jeon;Kim, Bok Kyu;Kil, Ki Jung
    • The Korea Journal of Herbology
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    • v.28 no.1
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    • pp.33-42
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    • 2013
  • Objective : Morus alba Linne Root Bark (MRAL) is a medicinal herb in Korean Medicine, known for its anti-inflammatory and anti-allergic properties. However, its mechanisms of action and the cellular targets have not yet been found and the study was developed to investigate the allergic suppressive effect of MRAL. The purpose of this study is to investigate the allergic suppressive effects of MRAL on activation of MC/9 mast cells. Methods : Cytotoxic activity of MRAL (50, 100, 200, 400 ${\mu}g/mL$) on MC/9 mast cells measured using EZ-Cytox cell viability assay kit (WST reagent). The levels of interleukin-5 (IL-5), IL-13 and IL-4, IL-5, IL-6, IL-13 mRNA expression were measured by enzyme-linked immunosorbent assay (ELISA) and real-time PCR respectively. The expression of transcription factors such as GATA-1, GATA-2, NFAT, AP-1 and NF-${\kappa}B$ p65 DNA binding activity were measured by western blot and electrophoresis mobility shift assay (EMSA). Results : Our results indicated that MRAL (50 ${\mu}g/mL$, 100 ${\mu}g/mL$) significantly inhibited PMA/Ionomycin-induced production of IL-5 and IL-13 and the expression of IL-4, IL-5, IL-6 and IL-13 mRNA in MC/9 mast cells. Moreover, MRAL (50 ${\mu}g/mL$, 100 ${\mu}g/mL$) inhibited PMA/Ionomycin-induced GATA-1, GATA-2, NFAT-1, NFAT-2, c-Fos protein expression and NF-${\kappa}B$ p65 DNA binding activity in MC/9 mast cells. Conclusions : In conclusion, we suspect the anti-allergenic activities of MRAL, may be related to the regulation of transcription factors GATA-1, GATA-2, NFAT-1, NFAT-2, c-Fos and NF-${\kappa}B$ p65 DNA binding assay causing inhibition of Th2 cytokines IL-5 and IL-13 in mast cells.

Inhibitory Effect of Inflammatory Cytokines Secretion of Cheonggeumganghwa-tang in Mast cell (비만세포에서의 청금강화탕의 염증성 세포활성물질 분비 억제 효과)

  • Choi Young Soo;Moon Goo;Kim Dong Woung;Han Se Hee;Won Jin Hee
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.3
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    • pp.887-892
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    • 2004
  • Cheonggeumganghwa-tang(CGT) has been used for the purpose of prevention and treatment of bronchial asthma and allergic asthma in Korea. To investigate the biological effect of CGT, the author examined cytotoxicity and inflammatory cytokines secretion with human mast cell line, HMC-1. HMC-1 was stimulated with phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187. CGT by itself had no effect on viability of HMC-1. The effects of CGT on the secretion of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 from HMC-1 were evaluated with enzyme-linked immunosorbent assay (ELISA). CGT (1 ㎎/㎖) inhibited PMA plus A23187 -induced TNF-α and IL-6 secretion, by 93.86 ± 2.05%, 68.69 ± 2.86%, respectively. CGT also inhibited the NF-κB (p50) expression. Taken together, these results suggest that CGT inhibit the production of inflammatory cytokines in HMC-1 cells through blockade of NF-κB activation.

Swiprosin-1 Regulates Cytokine Expression of Human Mast Cell Line HMC-1 through Actin Remodeling

  • Ramesh, T.P.;Kim, Young-Dae;Kwon, Min-Sung;Jun, Chang-Duk;Kim, Sang-Wook
    • IMMUNE NETWORK
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    • v.9 no.6
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    • pp.274-284
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    • 2009
  • Background: Swiprosin-1 was identified in human CD8+ lymphocytes, mature B cells and non-lymphonoid tissue. We have recently reported that swiprosin-1 is expressed in mast cells and up-regulated in both in vitro and in vivo. Methods: The expression of cytokines and swiprosin-1 were determined by by real time PCR and conventional PCR. Pharmacological inhibitors were treated to investigate potential mechanism of swiprosin-1 in mast cell activation. Actin content was evaluated by confocal microscopy and flow cytometry. Results: The swiprosin-1 augmented PMA/A23187-induced expression of cytokines and release of histamine. However, knock-down of swiprosin-1 showed only a modest effect on PMA/A23187-induced cytokine expression, suggesting that swiprosin-1 has gain-of-function characteristics. Swiprosin-1 was found in microvilli-like membrane protrusions and highly co-localized with F-actin. Importantly, either disruption of actin by cytochalasin B or inhibition of PI3 kinase, an enzyme involved in actin remodeling, by wortmannin blocked cytokine expression only in swiprosin-1-overexpressing cells. Conclusion: These results suggest that swiprosin-1 modulates mast cell activation potentially through actin regulation.

Gingivitis reducing effect of calcium glycerophosphate, cetylpyridinium chloride and dipotassium glycyrrhizate containing dentifrice (글리세로인산칼슘과 염화세틸피리디늄 및 글리시리진산이칼륨 배합세치제의 치은염 감소효과)

  • Kim, Sang-Sun;Cho, Ja-Won;Lee, Cheon-Hee
    • Journal of Korean society of Dental Hygiene
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    • v.17 no.6
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    • pp.983-992
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    • 2017
  • Objectives: This study is to compare measuring gingival and peridontal indices and changes in dental plaque per period using a three mix types of dentifrice and to investigate dental diseases preventive effects depending on gingivitis reducing effect of dentifrice through a clinical experiment. Methods: This study targeted adult females and males with mild to moderate gingivitis from age 20 to 60. The Calculus index, Papillary Marginal Attached Gingival (PMA) index, Gingival index, Patient Hygiene Performance (PHP) index, and Plaque index were measured at pre-experiment and at 1, 2, 4 weeks post experiment. Results: The PMA, Gingival index, PHP index, plaque index of experimentla group decreased after 4 weeks (p<0.05). Conclusions: A three mix types of dentifrice for relieving tooth sensitivity was verified to be effective in removing dental plaque and reducing gingivitis.