• Title/Summary/Keyword: leukotrienes

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The Effects of Single Component of Ginsenosides on the Mechanism of Mediator Release in the Allergic Hypersensitivity (인삼 사포닌 단일물질이 알러지 과민반응의 매개체 유리기전에 미치는 영향)

  • Ro, Jai-Youl;Kim, Kyung-Hwan
    • The Korean Journal of Pharmacology
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    • v.30 no.2
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    • pp.243-254
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    • 1994
  • Inflammatory diseases, allergic and asthmatic disorders are caused by the mediator release from the activation of the phospholipase C (PLC), phospholipase D (PLD), methyltransferase or adenylate cyclase etc. during IgG or IgE cross-linking of high affinity receptors on mast cells or basophil surface. One important enzyme activated after IgG or IgE receptor cross-linking is PLD, the enzyme which converts phosphatidylcholine (PC) to phosphatidic acid (PA). Under the hypothesis that these may be some differences in mediator release according to the difference in PLD activity, we attempted to confirm the ginseng saponin effects on the PLD activity. We examined the PLD activity during the passively sensitized mast cell activation in the presence of single component of ginsenosides $(Rc,\;Rg_1,\;Rg_2,\;Rg_3)$. We also measured the amount of mediators (histamine and leukotrienes) released by stimulating with ovalbumin (OA) or calcium ionophore (CaI), Guinea Pig lung mast cells were purified using enzyme digestion, count current elutriation, and discontinuous Percoll density gradient. In purified mast cells prelabeled with $[^3H]$ arachidonic acid or $[^3H]$ palmitic acid, PLD activity was assessed more directly by the production of labeled PEt by PLD-mediated transphosphatidylation in the presence of ethanol. Histanine release was determined by Spectrophotofluorometry, and leukotrienes by radioimmunoassay. The PLD activity during the passively sensitized mast cell activation is increased up to $3{\sim}5times$. The PLD activity during the passively sensitized mast cell activation in the presence of all ginsenosides is decreased up to $4{\sim}11$ times. $Rg_l\;and\;Rg_2$ ginsenoside pretreatment decreased histamine and leukotrienes by 50% in the OA-induced or by 40% in the Cal-induced mast cell after passively sensitization. Rc pretreatment poorly decreased histamine but leukotrienes decreased by 70% in the OA-induced or by 35% in the Cal-induced mast cell. $Rg_3$ ginsenoside pretreatment increased histamine release without challenging OA or Cal but leukotrienes decreased. These observations indicate that single unit of ginsenosldes may be an important contributor to inhibit the release of histamine and leukotrienes in the guinea pig lung mast cells, that inhibits the PLD-mediated formation of DAG evoked by mast cell activation.

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The Inhibitory Mechanism of Aloe Component (NY945) on the Mediator Releases evoked with Mast Cell Activation (Aloe 성분 NY945의 항알러지 작용)

  • Ro Jai Youl
    • Proceedings of the Korean Society of Toxicology Conference
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    • 1997.05a
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    • pp.65-74
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    • 1997
  • By using guinea pig lung mast cells, this study aimed to examine the effects of Aloe component(NY945) on the mediator releases caused by mast cell activation, and also aimed to assess the effects of NY945 on the mechanism of mediator releases in the mast cell activation. We partially purified mast cells from guinea pig lung tissues by using the enzyme digestion, the rough and the discontinuous density percoll gradient method. Mast cells were sensitized with $IgG_1$ (anti-OA) and challenged with ovalbumin. Histamine was assayed by fluorometric analyzer, leukotrienes by radioimmunoassay The phospholipase D activity was assessed more directly by the production of labeled phosphatidylethanol or phosphatidylbutanol which was produced by phospholipase D-mediated transphosphatidylation in the presence of ethanol or butanol. The amount of mass 1,2-diacylglycerol was measured by the [$^3H$]1,2-diacylgycerol produced when prelabeled with [$^3H$]myristic acid. In the mast cells prelabeled with L-[$^3H$]methyl methionine the phospholipid methylation was assessed by measuring the incorporation of the [$^3H$]methyl moiety into phospholipids. Pretreatment of NY945(10$\mu$g) significantly decreased histamine and leukotrienes releases during mast cell activation. The decrease of histamine release was stronger than that of leukotrienes during mast cell activation. The phospholipase D activity increased by the mast cell activation was decreased by the dose-dependent manner in the pretreatment of NY945. The amount of mass 1,2-diacylglycerol produced by activation of mast cells were decreased in the pretreatment of NY945. NY945 pretreatment strongly inhibited the incorporation of the [$^3H$]methyl moiety into phospholipids. The data suggest that NY945 purified from Aloe inhibits in part an increase of 1,2-diacylglycerol which is produced by activating mast cells with antigen-antibody complexes which is mediated via phosphatidylcholine-phospholipise D and phosphatidylinositole-phospholipise C systems, and then followed by the inhibition of histamine release. Furthermore, NY945 reduces the phosphatidylcholine production by inhibiting the methyltransfsrase I and II, which decrease the conversion of phosphatidylcholine into arachidonic acid and inhibits the production of leukotrines.

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Physiologically Active Fatty Acids their Metabolism and Function (생리활성지방산;그 대사와 기능)

  • Mitsu, Kayama
    • Journal of the Korean Applied Science and Technology
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    • v.13 no.3
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    • pp.15-24
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    • 1996
  • Essentiality was proposed in the field of lipid by Burr and Burr in 1929. When rats were raised on the fat-free diet, their growth retarded and their skin and tails showed the characteristic deficient symptoms, which were relieved by the addition of ${\omega}6(n-6)$ polyunsaturated fatty acids as linoleic(LA) and arachidonic(AA) acids to the basal diet. LA is dehydrogenated to ${\gamma}-linolenic$ acid(GLNA) by ${\Delta}6$ desaturase, then GLNA is 2 carbon chain elongated by elongase to $dihomo-{\gamma}-linolenic$ acid(DGLNA), which is desaturated by ${\Delta}5$ desaturase to AA. These acids are called LA family or ${\omega}6(n-6)$ polyunsaturated fatty acids(PUFA). ${\alpha}-Linolenic$ acid(ALNA) is converted through the series of desaturation and elongation steps to docosahexaenic acid(DHA) via eicosapentaenoic acid(EPA). These acids belong to ALNA family or ${\omega}3(n-3)$PUFA. Human who consume large amounts of EPA and DHA, which are present in fatty fish and fish oils, have increased levels of these two fatty acids in their plasma and tissue lipids at the expense of LA and AA. Alternately, vegetarians, whose intake of LA in high, have more elevated levels of LA and AA and lower levels of EPA and DHA in plasma lipids and in cell membranes than omnivores. AA and EPA are metabolized to substances called eicosanoids. Those derived form AA are known as prostanocids(prostaglandins and prostacyclins) of the 2-types and leukotrienes of the 4-series, whereas those derived from EPA are known as prostanoids of the 3-types and leukotrienes of the 5-series. DGLNA is a precursor of the 1-types of prostaglandins. The metabolites of AA and EPA have competitive functions. Ingestion of EPA from fish or fish oil replaces AA from membrane phospholipids in practically all cells. So this leads to a more physiological state characterized by the production of proatanoids and leukotrienes that have antithrombic, antichemotactic, antivasoconstrictive and antiinflammatory properties. It is evident that ${\omega}3$ fatty acids can affect a number of chronic diseases through eicosanoids alone.

The Inhibitory Mechanism of Aloe Glycoprotein (NY945) on the Mediator Release in the Guinea Pig Lung Mast Cell Activated with Antigen-Antibody Complexes

  • Ro, Jai-Youl;Lee, Byung-Chul;Chung, Myung-Hee;Lee, Seung-Ki;Sung, Chung-Ki;Kim, Kyung-Hwan;Park, Young-In
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.1
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    • pp.119-131
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    • 1998
  • It has been reported that the glycoprotein extracted from Aloe has strong anti-inflammatory response. However, there has been no research report yet about the effect of Aloe on allergic hypersensitivity reactivity. By using guinea pig lung mast cells, this study aimed to examine the effects of Aloe glycoprotein (NY945) on the mediator releases caused by mast cell activation, and also aimed to assess the effects of NY945 on the mechanism of mediator releases in the mast cell activation. We partially purified mast cell from guinea pig lung tissues by using the enzyme digestion, the rough and the discontinuous density percoll gradient method. Mast cells were sensitized with IgG1 (anti-OA) and challenged with ovalbumin. Histamine was assayed by fluorometric analyzer, leukotrienes by radioimmunoassay. The phospholipase D activity was assessed by the production of labeled phosphatidylalcohol. The amount of mass 1, 2-diacylglycerol (DAG) was measured by the $[^3H]DAG$ produced when prelabeled with $[^3H]myristic$ acid. The phospholipid methylation was assessed by measuring the incorporation of the $[^3H]methyl$ moiety into phospholipids of cellular membranes. Pretreatment of NY945 (10 ${\mu}g$) significantly decreased histamine and leukotrienes releases during mast cell activation. The decrease of histamine release was stronger than that of leukotriene during mast cell activation. The phospholipase D activity increased by the mast cell activation was decreased by the dose-dependent manner in the pretreatment of NY945. The amount of DAG produced by PLC activity was decreased by NY945 pretreatment. The amount of mass 1, 2-diacylglycerol produced by activation of mast cells was decreased in the pretreatment of NY945. NY945 pretreatment strongly inhibited the incorporation of the $[^3H]methyl$ moiety into phospholipids. The data suggest that NY945 purified from Aloe inhibits in part an increase of 1, 2-diacylglycerol which is produced by activating mast cells with antigen-antibody reactions, which is mediated via phosphatidylcholine-phospholipase D and phosphatidylinositol-phospholipase C systems, and then followed by the inhibition of histamine release. Furthermore, NY945 reduces the production of phosphatidylcholine by inhibiting the methyltransferase I and II, which decreases the conversion of phosphatidylcholine into arachidonic acid and inhibits the production of leukotrienes.

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Effects of Ginsenosides on the Mechanism of Histamine Release in the Guinea Pig Lung Mast Cells Activated by Specific Antigen-Antibody Reactions

  • Ro, Jai-Youl;Ahn, Young-Soo;Kim, Kyung-Hwan
    • The Korean Journal of Physiology and Pharmacology
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    • v.1 no.4
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    • pp.445-456
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    • 1997
  • We previously reported that some components of ginsenosides decreased mediator releases evoked by the activation of mast cells with specific antigen-antibody reactions. This study aimed to assess the effects of ginsenosides ($Rb_2$, Re) on the mechanism of histamine release in the mast cell activation. We partially purified guinea pig lung mast cells by using enzyme digestion, the rough and the discontinuous percoll density gradient method. Mast cells were sensitized with $IgG_1$ and challenged with ovalbumin (OA). Histamine was assayed by fluorometric analyzer, leukotrienes by radioimmunoassay. Phospholipase D (PLD) activity was assessed more directly by the production of $[^3H]phosphatidylbutanol$ (PBut) which was produced by PLD-mediated transphosphatidylation in the presence of butanol. The amount of 1,2- diacylglycerol (DAG) were measured by the $[^3H]DAG$ labeled with $[^3H]palmitic$ acid or $[^3H]myristic$ acid. Pretreatment of $Rb_2$ ($300\;{\mu}g$) significantly decreased histamine release by 60%, but Re ($300\;{\mu}g$) increased histamine release by 34%. Leukotrienes release in $Rb_2$ was decreased by 40%, Re was not affected in the leukotrienes release during mast cell activations. An increasing PLD activity during mast cell activation was decreased by the dose-dependent manner in the pretreatment of $Rb_2$, but Re pretreatment facilitated the increased PLD activity during mast cell activation. The amount of DAG produced by phospholipase C (PLC) activity was decreased by $Rb_2$ pretreatment, but Re pretreatment was not affected. The amount of mass DAG was decreased by $Rb_2$ and Re pretreatment during mast cell activation. The data suggest that $Rb_2$ purified from Korean Red Ginseng Radix inhibits the DAG which is produced by the activation of mast cells with antigen-antibody reactions via both phosphatidylinositide-PLC and phosphatidylcholine-PLD systems, and then followed by the inhibition of histamine release. However, Re increases histamine release by stimulation of DAG production, which is mediated by phosphatidylcholine-PLD system rather than by phosphatidylinositide-PLC system, but inhibits the mass DAG production. Thus, it could be inferred that other mechanisms play a role in the increase of histamine release during mast cell activation.

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Leukotriene Synthesis in Response to A23187 Is Inhibited by Methyl-β-Cyclodextrin in RBL-2H3 Cells

  • You, Hye Jin;Seo, Ji-Min;Moon, Ji-Young;Han, Sung-Sik;Ko, Young-Gyu;Kim, Jae-Hong
    • Molecules and Cells
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    • v.23 no.1
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    • pp.57-63
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    • 2007
  • Leukotrienes (LTs) are produced by several biosynthetic enzymes including cytosolic phospholipase $A_2$ ($cPLA_2$), 5-lipoxygenase (5-LO), and 5-lipoxygenase activating protein (FLAP) in the perinuclear area. In the present study, we showed that pretreatment with methyl-${\beta}$-cyclodextrin (MβCD), a cholesterol-depleting agent, dramatically reduced the synthesis of LTs in response to A23187 in mast cells. A23187-induced LT synthesis was inhibited by pretreatment with M${\beta}$CD, and this effect was reversed when cholesterol was added. In an approach to identifying the $M{\beta}CD$-sensitive protein(s), we observed that FLAP co-localized with flotillin-1, a lipid raft marker protein, in the lipid raft-rich low-density region of sucrose gradients. In addition, electron microscopic analysis revealed that FLAP co-localized with flotillin-1. Together, these results suggest that FLAP is present in cholesterol-rich lipid raft-like domains and that its localization in these domains is critical for LT synthesis.

The Regulatory Role of 5-Lipoxygenase in Mature Osteoclasts (5-Lipoxygenase에 의한 성숙 파골세포의 조절)

  • Noh, A Long Sae Mi;Moon, Miran;Jeong, Ji-Eun;Yim, Mijung
    • YAKHAK HOEJI
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    • v.56 no.6
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    • pp.347-351
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    • 2012
  • 5-Lipoxygenase (5-LO) catalyzes the formation of two major groups of leukotrienes, LTB4 and cysteinyl leukotrienes (CysLT), and it has been implicated as a promising drug target to treat various inflammatory diseases. Since its role in mature osteoclasts (mOCs) had not been reported, we investigated the effect of 5-LO inhibitors on mOCs. We showed that 5-LO inhibitors dose-dependently decreases the number of mOCs. The effects of 5-LO inhibitors were reversible, suggesting that they did not cause any cellular damages in mOCs. We further demonstrated that the suppression of mOCs by 5-LO inhibitors was caused mainly by disruption of the actin ring formation. Similar effects were shown with CysLT receptor (CysLTR)1 antagonist in mOCs. The mRNA expression of CysLTR1 and the production of CysLT were increased in mOCs. These results indicate that CysLTR1 mediates the suppression of mOCs by 5-LO inhibitors. Taken together, this study demonstrated that 5-LO plays important role in mOCs and possibly a novel therapeutic target for bone resorption diseases.

Effects of Phyto-Extract Mixture (PEM381) in Type I Allergic Reaction-Induced Mice (제 I 형 알레르기 반응이 유도된 생쥐에서 식물추출 복합물(PEM381)의 효과)

  • Kim, Kyung-Bum;Park, Jeong-Su;Jeong, Jong-Moon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.11
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    • pp.1377-1384
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    • 2007
  • A previous study suggested that the phyto-extract mixture (PEM381) containing Camellia sinensis (leaf), Psidium guajava (leaf), and Rosa hybrida (flower) inhibited not only arachidonic acid cascade-related enzymes (5-lipoxygenase and cyclooxygenase) in vitro but also degranulation and histamine release from rat peritoneal mast cells. In this study, the same PEM381 was used to investigate its inhibitory effects on the syntheses of leukotrienes and prostaglandins as well as on serum concentration of histamine and eosinophils infiltration in type I allergic reaction-induced mice. The PEM381 could decrease concentrations of serum cysteinyl leukotrienes from mice activated by anti-DNP IgE and DNP-albumin. The concentration of serum histamine by oral administration of PEM381 (25, 50, and 100 mg/kg of body weight) in type I allergic reaction-induced mice was $395.93{\pm}190.37$ nM, $315.59{\pm}164.23$ nM, and $325.07{\pm}112.02$ nM, respectively, while that of positive control (promethazine hydrochloride 10 mg/kg of body weight) was $270.12{\pm}24.02$ nM. In addition, the PEM381 also showed inhibitory effect on the eosinophils infiltration in the nasal mucosa of mice which were sensitized with ovalbumin. However, the effect of PEM381 on the syntheses of prostaglandins seemed to be insignificant. Consequently, these results suggest that PEM381 may be useful for the prevention and treatment of type I allergy-related diseases.

Lysophosphatidic Acid and Lysophosphatidylserine, New Bioactive Lysophospholipids

  • Arai, Hiroyuki
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.109-110
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    • 2003
  • Phospholipids function as major components of biological membranes as well as precursors of biologically active lipid messengers. It is well known that arachidonic acid attached at the sn-2 position of phosphoglycerides serves as a precursor of prostaglandins and leukotrienes. Recently, it has been recognized that lysophospholipids such as lysophosphatidic acid, sphingosine 1-phosphate, lysophosphatidylserine and monoglyceride also function as lipid messengers with a variety of biological activities. (omitted)

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Cromakalim Blocks Membrane Phosphoinositide Activated Signals in the Guinea Pig Lung Mast Cells Stimulated with Antigen-Antibody Reactions

  • Ro, Jai-Youl;Kim, Ji-Young;Kim, Kyung-Hwan
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.2
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    • pp.251-260
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    • 1998
  • Cromakalim (BRL 34915), known as an airway smooth muscle relaxant, inhibited the releases of mediators in the antigen-induced mast cell activation. It has been suggested that cromakalim, in part, inhibited mediator releases by inhibiting the initial increase of 1,2-diacylglycerol (DAG) produced by the activation of the other phospholipase system which is different from phosphatidylcholine-phospholipase D pathway. The aim of this study is to further examine the inhibitory mechanism of cromakalim on the mediator release in the mast cell activation. Guinea pig lung mast cells were purified by using enzyme digestion and percoll density gradient. In purified mast cells prelabeled with $[^3H]PIP_2$, phospholipase C (PLC) activity was assessed by the production of $[^3H]$insitol phosphates. Protein kinase C (PKC) activity was assessed by measuring the protein phosphorylated from mast cells prelabeled with $[{\gamma}-32P]ATP$, and Phospholipase $A_2\;(PLA_2)$ activity by measuring the lyso-phosphatidylcholine produced from mast cell prelabeled with 1-palmitoyl-2-arachidonyl $phosphatidyl-[^{14}C]choline$. Histamine was assayed by fluorometric analyzer, and leukotrienes by radioimmunoassay. The PLC activity was increased by activation of the passively sensitized mast cells. This increased PLC activity was decreased by cromakalim pretreatment. The PKC activity increased by the activation of the passively sensitized mast cells was decreased by calphostin C, staurosporine and cromakalim, respectively. The $PLA_2$ activity was increased in the activated mast cells. The pretreatment of cromakalim did not significantly decrease $PLA_2$ activity. These data show that cromakalim inhibits histamine release by continuously inhibiting signal transduction processes which is mediated via PLC pathway during mast cell activation, but that cromakalim does not affect $PLA_2$ activity related to leukotriene release.

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