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Hyo-Hyun Park,
Mi Jin Kim,
Ying Li,
Young Na Park,
Jiean Lee,
Youn Ju Lee,
Sun-Gun Kim,
Hyun-Je Park,
Jong Keun Son,
Hyeun Wook Chang, Eunkyung Lee
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ABSTRACT: Little is known about the biological properties of britanin, which is isolated from the flowers of Inula japonica (Inulae Flos). Based on our previous studies that Inulae Flos had anti-inflammation and anti-asthmatic activities, we tried to find the bioactive compounds from it. In this study, the anti-inflammatory effects of britanin on the inflammatory mediators as well as on nuclear factor (NF)-кB and mitogen-activated protein (MAP) kinase activation were evaluated in RAW 264.7 cells. Britanin inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE(2)) along with the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. In addition, britanin reduced the release of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6. Furthermore, the phosphorylations of MAP kinases (p38 and JNK) in LPS-stimulated RAW 264.7 cells were suppressed by britanin. Moreover, britanin inhibited the NF-κB activation induced by LPS, which was associated with the abrogation of IκBα degradation and subsequent decreases in nuclear p65 levels. This study suggests that the anti-inflammatory activities of britanin might be attributed to the inhibition of iNOS and COX-2 and cytokine expression at least in part, through the attenuation of the phosphorylations of MAP kinases and NF-κB activation via IκBα degradation in macrophages. We conclude that britanin may have potential for the treatment of inflammatory diseases through the down-regulation of MAP kinases and NF-κB mediated activation of macrophages.
International immunopharmacology 12/2012; · 2.21 Impact Factor
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Yue Lu,
Ying Li,
Meihua Jin,
Ju Hye Yang,
Xian Li,
Guang Hsuan Chao,
Hyo-Hyun Park,
Young Na Park,
Jong Keun Son, Eunkyung Lee,
Hyeun Wook Chang
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ABSTRACT: The flowers of Inula japonica (Inulae Flos) have long been used in traditional medicine for the treatment of bronchitis, digestive disorders, and inflammation. However, the mechanisms underlying its anti-inflammatory effects remain yet to be elucidated. The objectives of this study were 1) to assess the anti-allergic activity of the ethanol extract of flowers of Inula japonica extract (IFE) in vivo, 2) to investigate the mechanism of its action on mast cells in vitro, and 3) to identify its major phytochemical compositions.
The anti-allergic activity of IFE was evaluated using mouse bone marrow-derived mast cells (BMMCs) in vitro and a passive cutaneous anaphylaxis (PCA) animal model in vivo. The effects of IFE on mast cell activation were evaluated in terms of degranulation, eicosanoid generation, Ca(2+) influx, and immunoblotting of various signaling molecules.
IFE inhibited degranulation and the generation of eicosanoids (PGD(2) and LTC(4)) in stem cell factor (SCF)-stimulated BMMCs. Biochemical analysis of the SCF-mediated signaling pathways demonstrated that IFE inhibited the activation of multiple downstream signaling processes including mobilization of intracellular Ca(2+) and phosphorylation of the mitogen-activated protein kinases (MAPKs), PLCγ1, and cPLA(2) pathways. When administered orally, IFE attenuated the mast cell-mediated PCA reaction in IgE-sensitized mice. Its major phytochemical composition included three sesquiterpenes, 1-O-acetylbritannilactone, britanin and tomentosin.
This study suggests that IFE modulates eicosanoids generation and degranulation through the suppression of SCF-mediated signaling pathways that would be beneficial for the prevention of allergic inflammatory diseases. Anti-allergic activity of IFE may be in part attributed particularly to the presence of britanin and tomentosin as major components evidenced by a HPLC analysis.
Journal of ethnopharmacology 06/2012; 143(1):151-7. · 2.32 Impact Factor
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Young Na Park,
Youn Ju Lee,
Jeon Hyeun Choi,
Meihua Jin,
Ju Hae Yang,
Ying Li,
Jiean Lee,
Xian Li,
Keuk-Jun Kim,
Jong Keun Son,
Hyeun Wook Chang,
Jong Yeon Kim, Eunkyung Lee
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ABSTRACT: The flowers of Inula japonica (Inulae Flos) have long been used in traditional medicine for treating inflammatory diseases. The effects on OVA-induced asthmatic mice of an Inulae Flos extract (IFE) were evaluated in this study. The anti-asthmatic effects of IFE were determined by observing eosinophil recruitment, airway hyper-responsiveness (AHR), Th2 cytokine and IgE levels, and lung histopathology. The IFE treatment effectively reduced the percentage of eosinophils and Th2 cytokines in the bronchoalveolar lavage fluid (BALF) when compared to the levels in OVA-induced mice. IFE also suppressed AHR induced by aerosolized methacholine in OVA-induced mice. The results of the histopathological studies indicate that inflammatory cell infiltration and mucus hypersecretion were both inhibited by the IFE administration when compared to the effect on OVA-induced mice. The IFE treatment also suppressed the serum IgE levels and decreased Th2 cytokines in the supernatant of cultured splenocytes. These results suggest that IFE may have therapeutic potential against asthma.
Bioscience Biotechnology and Biochemistry 05/2011; 75(5):871-6. · 1.28 Impact Factor
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ABSTRACT: The flowers of Inula japonica (Inulae Flos) have long been used in traditional medicine for the treatment of inflammatory diseases. In the present study, we investigated the anti-inflammatory properties of Inulae Flos Extract (IFE).
The anti-inflammatory effects of IFE against nitric oxide (NO), PGE(2), TNF-α, and IL-6 release, as well as NF-κB and MAP kinase activation were evaluated in RAW 264.7 cells.
IFE inhibited the production of NO and the expression of inducible nitric oxide synthase (iNOS) in LPS-stimulated RAW264.7 cells. In addition, IFE reduced the release of pro-inflammatory cytokines, such as TNF-α and IL-6. Furthermore, IFE inhibited the NF-κB activation induced by LPS, which was associated with the abrogation of IκB-α degradation and subsequent decreases in nuclear p65 and p50 levels. Moreover, the phosphorylation of ERK, JNK, and p38 MAP kinases in LPS-stimulated RAW 264.7 cells was suppressed by IFE in a dose-dependent manner.
These results suggest that the anti-inflammation activities of IFE might be attributed to the inhibition of NO, iNOS and cytokine expression through the down-regulation of NF-κB activation via suppression of IκBα and MAP kinase phosphorylation in macrophages.
Immune Network 10/2010; 10(5):145-52.
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ABSTRACT: Intercellular adhesion molecule-1 (ICAM-1) is associated with processes of inflammation. We investigated the effects of deoxypodophyllotoxin (DPT) on tumor necrosis factor-alpha (TNF-alpha) induced ICAM-1 expression in the mouse lung epithelial cell line, LA4. DPT (5 to 20 nM) inhibited TNF-alpha-induced ICAM-1 expression through nuclear factor-kappa B (NF-kappaB) in a dose-dependent manner and repressed ICAM-1 promoter activity. NF-kappaB reporter gene activity and DNA binding activity were also strongly inhibited. In addition, DPT inhibited degradation by the TNF-alpha induced inhibitory kappaB-alpha (IkappaB-alpha) in a concentration-dependent manner. Taken together with our previous results suggest DPT might provide a basis for novel anti-inflammatory drug development.
Biological & Pharmaceutical Bulletin 01/2010; 33(1):1-5. · 1.66 Impact Factor
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ABSTRACT: Previously, we reported that an ethanol extract of Ailanthus altissima has antiinflammatory activity in an ovalbumin (OVA)-sensitized murine asthmatic model. To determine the biological compounds from this plant, luteolin-7-O-glucoside (L7G) was isolated and its antiasthmatic activity was evaluated in an in vivo murine asthmatic model. L7G (10 to 100 mg/kg, per os (p.o.)) reduced the amount of eosinophil infiltration in bronchoalveolar lavage (BAL) fluid in a dose-dependent manner. In comparison, dexamethasone (5 mg/kg, p.o.), which was used as a positive control, also strongly inhibited the number of infiltrating eosinophils. L7G inhibited both the prostaglandin E(2) (PGE(2)) and serum immunoglobulin E level in BAL fluid in a dose-dependent manner. In addition, L7G inhibited the transcript profiles of interleukin (IL)-4, IL-5, and IL-13 mRNA expression levels in the murine asthma model, as determined using reverse transcription-polymerase chain reaction (RT-PCR). These results suggest that the antiasthmatic activity of L7G in OVA-induced lung inflammation may occur in part via the downregulation of T helper 2 cytokine transcripts as well as the inhibition of PGE(2) production.
Biological & Pharmaceutical Bulletin 10/2009; 32(9):1500-3. · 1.66 Impact Factor
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ABSTRACT: Ym1 and Ym2 (Ym1/2) are chitinase-like proteins and we reported previously that IL-4 induced Ym1/2 in mouse bone marrow-derived mast cells. In the present study, ovalbumin-induced asthmatic mice were used to investigate the effect of glucocorticoids on Ym1/2 expression. Ym1/2 were highly induced in bronchoalveolar lavage fluid (BALF) and the lung. Ym1/2 expression was completely inhibited by dexamethasone (Dex) in BALF and weakly inhibited in the lung. Primary cultured macrophages were used to investigate the inhibition of Ym1/2 expression at the cellular level. Although Dex pretreatment inhibited the Ym1/2 expression level in an animal model, it did not reduce IL-4 induction of Ym1/2 expression in vitro. Next, we tested whether Dex blocks IL-4 induced STAT6 signaling and found that it had no inhibitory effect on the phosphorylation level of STAT6 in macrophages. The luciferase reporter assay also revealed that Dex did not inhibit IL-4 induction of Ym1/2 promoter activity. These results indicate that the inhibitory effect of Dex on Ym1/2 protein expression in the murine model of asthma does not involve the STAT6 signaling pathway.
Biological & Pharmaceutical Bulletin 10/2008; 31(9):1663-6. · 1.66 Impact Factor
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Meihua Jin,
Tae Chul Moon,
Zhejiu Quan, Eunkyung Lee,
Yun Kyung Kim,
Ju Hae Yang,
Seok-Jong Suh,
Tae Cheon Jeong,
Seung Ho Lee,
Cheorl-Ho Kim,
Hyeun Wook Chang
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ABSTRACT: Deoxypodophyllotoxin (DPT), a naturally occurring flavolignan with anti-inflammatory activity, was isolated from Anthriscus sylvestris HOFFM., and we examined its effects on the expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated, murine macrophage-like RAW264.7 cells. Western blot analysis performed with specific anti-iNOS antibodies showed that a decrease in nitric oxide (NO) was accompanied by a decrease in the iNOS protein level. To clarify the mechanistic basis for DPT's ability to inhibit iNOS induction, we examined the effect of DPT on nuclear factor (NF)-kappaB transcriptional activity and DNA binding activity. DPT potently suppressed both reporter gene activity and DNA binding activity. These findings suggest that DPT in RAW264.7 cells abolished LPS-induced iNOS expression by inhibiting the transcription factor, NF-kappaB.
Biological & Pharmaceutical Bulletin 08/2008; 31(7):1312-5. · 1.66 Impact Factor
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ABSTRACT: Lipoic acid is an essential disulfide cofactor required for the lipoate-dependent enzymes including pyruvate dehydrogenase (PDH), alpha-ketoglutarate dehydrogenase (KGDH), and glycine cleavage enzymes that function in key metabolic pathways in most prokaryotes and eukaryotes. Lipoic acid is covalently bound to lipoate-dependent enzymes by lipoate-protein ligase or lipoate transferase. Here, we characterized a lipoyl-protein ligase A (OsLPLA) gene of rice. The OsLPLA gene, which encoded 270 amino acids, was located on an approximately 21 Mb of chromosome 8 on the physical map of Oryza sativa Japonica type. OsLPLA transcripts were abundantly expressed in leaves and developing seeds. The OsLPLA gene functionally complemented an Escherichia coli lplA null mutant. Furthermore, the protein expressed from the OsLPLA gene in an E. coli lplA mutant successfully transferred exogenous lipoate to lipoate-dependent enzymes, including the E2 subunits of the PDH, the E2 subunit of KGDH and the H-protein of glycine decarboxylase, confirming that rice OsLPLA successfully catalyzed covalent attachment of lipoate onto lipoate-dependent enzymes.
Gene 06/2007; 393(1-2):53-61. · 2.34 Impact Factor
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ABSTRACT: Methyl gallate (MG) is a medicinal herbal product that is isolated from Paeonia lactiflora that inhibits cyclooxygenase-2 (COX-2) dependent phases of prostaglandin D2 (PGD2) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with an IC50 values of 17.0 microM. This compound also found inhibited the COX-2-dependent conversion of the exogenous arachidonic acid to PGD2 in a dose-dependent manner with an IC50 values of 19.0 microM, using a COX enzyme assay kit. However, at concentrations up to 80 microM, MG did not inhibit COX-2 protein expression in BMMC, indicating that MG inhibits COX-2 activity directly. Furthermore, MG consistently inhibited the production of leukotriene C4 (LTC4) in a dose dependent manner, with an IC50 value of 5.3 microM. These results demonstrate that MG has a dual cyclooxygenase-2/5-lipoxygenase inhibitory activity, which might provide the basis for novel anti-inflammatory drugs.
Archives of Pharmacal Research 11/2006; 29(10):874-8. · 1.59 Impact Factor
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Chang Xin Lin, Eunkyung Lee,
Mei Hua Jin,
Jumin Yook,
Zhejiu Quan,
Kyungmi Ha,
Tae Chul Moon,
Mi Jin Kim,
Keuk Jun Kim,
Seung Ho Lee,
Hyeun Wook Chang
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ABSTRACT: The effect of deoxypodophyllotoxin (DPT) isolated from Anthriscus sylvestris Hoffm. was evaluated in an IN VIVO animal model for antiasthmatic activity. DPT (1.0 to 5 mg/kg) was given orally to ovalbumin (OVA)/alum-induced asthmatic mice. DPT reduced the number of infiltrated eosinophils in bronchoalveolar lavage (BAL) fluid in a dose-dependent manner. Dexamethasone (5 mg/kg), which was used as a positive control, also strongly inhibited the number of infiltrated eosinophils. The effect of DPT on a transcript profile in a murine asthma model was determined by RT-PCR, which showed that DPT decreased the mRNA levels of the Th2 cytokines. Northern blot analysis showed that DPT also reduced both the eotaxin and arginase I mRNA levels in a dose-dependent manner.
Planta Medica 08/2006; 72(9):786-91. · 2.15 Impact Factor
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ABSTRACT: As part of an ongoing investigation to find bioactive medicinal herbs exerting anti-inflammation activity, the effect of an ethanol extract from the parts of Ailanthus altissima (Simaroubaceae) was evaluated in both in vitro and in in vivo system. The ethanol extract of A. altissima (EAa) inhibited generation of the cyclooxygenase-2 (COX-2) dependent phases of prostaglandin D2 in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with an IC50 value of 214.6 microg/ml. However, this compound did not inhibit COX-2 protein expression up to a concentration of 400 microg/ml in the BMMC, indicating that EAa directly inhibits COX-2 activity. In addition, EAa inhibited leukotriene C4 production with an IC50 value of 25.7 microg/ml. Furthermore, this compound inhibited degranulation reaction in a dose dependent manner, with an IC50 value of 27.3 microg/ml. Ovalbumin (OVA)-sensitized mice were orally pretreated with EAa before aerosol challenges. EAa reduced the eosinophil infiltration into the airway and the eotaxin, IL-4, and IL-13 mRNA expression levels. These results suggest that the anti-inflammation activity of A. altissima in OVA-induced lung inflammation may occur in part via the down regulation of T(H)2 cytokines and eotaxin transcripts as well as the inhibition of inflammatory mediators.
Biological & Pharmaceutical Bulletin 06/2006; 29(5):884-8. · 1.66 Impact Factor
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Eunkyung Lee,
Kyungmi Haa,
Ju Min Yook,
Mei Hua Jin,
Chang Seob Seo,
Kun Ho Son,
Hyun Pyo Kim,
Ki Hwan Bae,
Sam Sik Kang,
Jong Keun Son,
Hyeun Wook Chang
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ABSTRACT: As an attempt to find bioactive medicinal herbs exerting anti-asthmatic activity, the effects of an ethanol extract from the parts of Saururus chinensis were evaluated in both in vitro and in vivo. The ethanol extract of S. chinensis (ESC) inhibited generation of the cyclooxygenase-2 (COX-2) dependent phases of prostaglandin D(2) in bone marrow-derived mast cells in a concentration-dependent manner with an IC(50) value of 14.3 microg/ml. ESC also inhibited leukotriene C(4) production with an IC(50) value of 0.3 microg/ml. This demonstrates that ESC has COX-2/5-lipoxygenase dual inhibitory activity. In addition, this compound inhibited degranulation reaction in a dose dependent manner, with an IC(50) value of 1.3 microg/ml. An ovalbumin induced mouse asthmatic animal model was used to determine its in vivo anti-asthmatic activity. The oral administration (50-200 mg/kg) of ESC reduced the number of infiltrated eosinophil in a bronchoalveolar lavage fluid. Furthermore, ESC (100 mg/kg) inhibited the eotaxin and IL-4 mRNA expression levels. These results suggest that the anti-asthmatic activity of S. chinensis might in part occur via the inhibition of eicosanoid generation, degranulation as well as the down regulation of IL-4 and eotaxin mRNA expression.
Biological & Pharmaceutical Bulletin 03/2006; 29(2):211-5. · 1.66 Impact Factor
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ABSTRACT: Ginkgetin, a biflavone from Ginkgo biloba leaves, was previously reported to be a phospholipase A(2) inhibitor and this compound showed the potent antiarthritic activity in rat adjuvant-induced arthritis as well as analgesic activity. This investigation was carried out to find effects on cyclooxygenase-2 (COX-2) in vitro effect. Ginkgetin inhibits COX-2 dependent phases of prostaglandin D(2) (PGD(2)) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with IC(50) values of 0.75 microM. Western blotting probed with specific anti-COX-2 antibodies showed that the decrease in quantity of the PGD(2) product was accompanied by a decrease in the COX-2 protein level. In addition, this compound consistently inhibited the production of leukotriene C(4) (LTC(4)) in a dose dependent manner, with an IC(50) value of 0.33 microM. These results demonstrate that ginkgetin has a dual cyclooxygenase-2/5-lipoxygenase inhibitory activity. Furthermore, this compound also inhibited degranulation reaction in a dose dependent manner, with an IC(50) value of 6.52 microM. Therefore, this compound might provide a basis for novel anti-inflammatory agents.
Biological & Pharmaceutical Bulletin 01/2006; 28(12):2181-4. · 1.66 Impact Factor
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ABSTRACT: Mast cells play an important role in allergic inflammation by releasing various bioactive mediators. The function of mast cells is enhanced by various stimuli, partly due to the induction of specific genes and their products. Although many inducible genes have been identified, a significant number of genes remain to be identified. Therefore, this study used PCR-selected cDNA subtraction to establish the profile of induced genes in the connective tissue (CT) type-like mast cells derived from bone marrow cells cultured in the presence of IL-4 and stem cell factor. Two hundred and fifty cDNA clones were obtained from the CT type-like mast cells by PCR-selected cDNA subtraction. Among them, Ym1/2, a chitinase-like protein, is one of the most abundantly induced genes. Ym1 is produced by activated macrophages in a parasitic infection, whereas its isotype, Ym2, is highly upregulated in allergic lung disease. In order to differentiate which isotype is expressed in bone marrow cells, specific primers for bone marrow-derived mast cells (BMMC), and CT type-like mast cells were used for RT-PCR. The results showed that Ym1 was constitutively expressed in bone marrow cells and gradually decreased in the presence of IL-3, whereas Ym2 was induced only in the presence of IL-4. CT type-like mast cells from bone marrow cells expressed Ym1 throughout the culture period and Ym2 was induced only by the addition of IL-4 into BMMC, indicating that IL-4 is essential for the expression of Ym1/2 genes.
Immunology and Cell Biology 11/2005; 83(5):468-74. · 3.66 Impact Factor
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ABSTRACT: Platelet activating factor (PAF)-acetylhydrolase (PAF-AH) is an enzyme that hydrolyzes the acetyl ester at the sn-2 position of PAF, and converts it to the inactive metabolite, lyso PAF. This enzyme is distributed widely in the intracellular as well as the extracellular matrix and is believed to be a defense mechanism that protects the host against the toxic effects of PAF and other biologically active oxidized phospholipids. Purification and expression of cDNA cloning of the intracellular and extracellular types of PAF-AH from several sources from different species have been reported. In this study, the cDNA for PAF-AH was cloned by reverse transcription (RT)-PCR from total RNA of bovine mammary gland. The complete amino acid sequences from the cDNA contains 444 amino acids and was identical to that of the PAF-AH isolated from the bovine spleen cDNA library except for two mismatches of amino acid residues (Thr-247 to Met and Ile-431 to Thr). Recombinant PAF-AH was expressed in HEK 293 cells, which exhibited enzyme activity in the in vitro assay system. Furthermore, recombinant bovine PAF-AH was identified by western blot using human plasma PAF-AH antibody as a monomeric polypeptide with a molecular weight of approximately 43 kDa. This protein can be applied to in vivo models to test its protective role against the deleterious PAF actions.
Biological & Pharmaceutical Bulletin 05/2005; 28(4):580-3. · 1.66 Impact Factor
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ABSTRACT: Mast cells play an important role in allergic inflammation by releasing their bioactive mediators. The function of mast cells is enhanced by stimulation because of the induction of specific genes and their products. While many inducible genes have been elucidated, we speculated that a significant number of genes remain to be identified. Thus, we applied differential display (dd) PCR to establish a profile of the induced genes in bone marrow-derived mast cells (BMMCs) after they were co-cultured with 3T3 fibroblasts. To date, 150 cDNA fragments from the connective-type mast cells (CTMCs) were amplified. Among them, thirty cDNA fragments were reamplified for cloning and sequencing. The ddPCR strategy revealed that serine proteases were the most abundant genes among the sequenced clones induced during the maturation. Additionally, unknown genes from the co-culture of BMMCs with 3T3 fibroblasts were identified. We confirmed their induction in the CTMCs by Northern blot analysis and RT-PCR. Characterization of these induced genes during the maturation processes will provide insight into the functions of mast cells.
Archives of Pharmacal Research 03/2005; 28(2):232-7. · 1.59 Impact Factor
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ABSTRACT: This study examined the effect of a podophyllotoxin derivative, deoxypodophyllotoxin (anthricin), which is a medicinal herb product isolated from Anthriscus sylvestris Hoffm. Deoxypodophyllotoxin was tested in a rat PCA (passive cutaneous anaphylaxis) assay by administering deoxypodophyllotoxin intraperitoneally (1.0 to 10 mg/kg, i.p.) and intravenously (0.25 to 1.0 mg/kg, i.v.). Deoxypodophyllotoxin dose-dependently inhibited the PCA reaction activated by anti-dinitrophenyl (DNP) IgE. The PCA inhibitory activity of deoxypodophyllotoxin was stronger than those of prednisolone and indomethacin, which were used as positive controls. These results suggest that deoxypodophyllotoxin may be beneficial in regulating the immediate-type allergic reaction.
Planta Medica 06/2004; 70(5):474-6. · 2.15 Impact Factor
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ABSTRACT: Lipopolysaccharide (LPS)-stimulated macrophages produce large amounts of nitric oxide (NO) by inducible nitric oxide synthase (iNOS). This is an important mechanism in macrophage-induced septic shock and inflammation. In the present study, we tested a synthetic propenone compound, 1-furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) for its ability to inhibit the production of tumor necrosis factor-alpha (TNF-alpha) and an inducible enzyme, iNOS, in the LPS-stimulated murine macrophage-like cell line, RAW264.7. FPP-3 consistently inhibited nitric oxide (NO) and TNF-alpha production in a dose dependent manner, with IC(50) values of 10.0 and 13.1 microM, respectively. Western blotting probed with specific anti-iNOS antibodies showed that the decrease in quantity of the NO product was accompanied by a decrease in the iNOS protein level. In cells transiently transfected with nuclear factor (NF)-kappaB promoter-luciferase reporter construct, this compound clearly inhibited the LPS-stimulated NF-kappaB activation. Moreover, this compound inhibited IkappaB-alpha degradation in a concentration and time-dependent manner. These results indicate that FPP-3 inhibits NO production via inhibition of degradation of IkappaB-alpha through NF-kappaB activation.
Biological & Pharmaceutical Bulletin 06/2004; 27(5):617-20. · 1.66 Impact Factor
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ABSTRACT: We previously reported that rhIL-4 induced apoptosis and rhIL-6 mediated protection of human mast cells derived from cord blood mononuclear cells. Based on the result, we attempted to obtain the phenotypes and differentiation of CD3+ cells from cord blood by investigating their cell surface markers in the presence of rhSCF plus rhIL-4. The effect of co-cultured CD3+ cells on fetal liver mast cells (FLMCs) was also determined. Phenotypes from cord blood-derived cells were analyzed by flow cytometry and cell numbers were determined. Fetal liver mast cells were cultured with cord blood-derived cells (mainly CD3+) in the presence of rhSCF and/or rhIL-4 and were analyzed to determine cell number and expression of Kit+ and FcepsilonR1. The percentage of CD3+ cells from cord blood-derived cells on day 0 was about 41 +/- 13.5%, following monocytes and granulocytes. CD3+ cells increased in number (1.5-fold) and purity (90%), whereas other cell types did not survive. More than 60% of CD3+ cells from cord blood at day 0 were CD4(-)CD8-. These double-negative cells dramatically decreased by 1 week of culture, while CD4+CD8+ cells increased in number and purity through 3 weeks of culture, and then decreased as greater numbers of single-positive T cells emerged. We also found that FcepsilonR expression on FLMC increased in the presence of rhIL-4, but was not affected by the T cells that developed from cord blood mononuclear cells. The results indicate that IL-4, a Th2 type cytokine, together with rhSCF, can induce T cell proliferations, differentiation, and maturation from cord blood progenitor cells.
Cellular Immunology 12/2003; 226(1):30-6. · 1.97 Impact Factor
