Biomedical subjects

Suhkneung Pyo

Publications and source records attributed to Suhkneung Pyo.

At least 19 recordsLinked to original sources

PubMed2006

Allicin, a major component of garlic, inhibits apoptosis of macrophage in a depleted nutritional state.

OBJECTIVE: Allicin is believed to be the main component responsible for the biological activity of garlic. The regulation of cell death might have therapeutic potential in many diseases, and previous studies have demonstrated that allicin stimulates the functional activity of macrophages. Therefore, this study examined the effects of allicin on the apoptosis of macrophages induced by serum- and amino acid-free culture. METHODS: The apoptosis of peritoneal macrophages was examined after pretreating them with allicin and incubating them in a depleted nutritional state. The rate of apoptosis was determined using propidium iodide staining analysis using flow cytometry, DNA fragmentation, and a caspase-3 assay. Western blot analysis was used to examine the changes in the pro- or antiapoptotic protein expression levels. RESULTS: DNA fragmentation and propidium iodide staining analyses revealed that allicin decreased the malnutrition-induced apoptosis of macrophages. The level of Bax expression, the amount of cytochrome-c released from the mitochondria, and the caspase-3 activity were also lower in the allicin-treated macrophages than in the untreated macrophages in a depleted nutritional state. Moreover, the MEK (mitogen-activated protein kinase/extracellular signal-regulated kinase-kinase) inhibitor suppressed the allicin-induced inhibition of apoptosis in a depleted nutritional state and allicin increased the level of ERK1/2 phosphorylation. CONCLUSION: Allicin inhibits the apoptosis of macrophages in a depleted nutritional state through the MEK/extracellular signal-regulated kinase pathway.

Animals↗

PubMed2006

Inhibition of ICAM-1 expression by garlic component, allicin, in gamma-irradiated human vascular endothelial cells via downregulation of the JNK signaling pathway.

Ionizing radiation used in cancer therapy frequently exerts damaging effects on normal tissues and induces a complex response including inflammation. Since the upregulation of adhesion molecules on endothelial cell surface has been known to be associated with inflammation and our previous data showed that irradiation enhanced adhesion molecules expression, interfering with the expression of adhesion molecules may be an important therapeutic target of inflammatory diseases. We examined the effect of allicin, a major component of garlic, on the induction of intercellular adhesion molecule-1 (ICAM-1) by gamma-irradiation (gamma IR) and the mechanisms of its effect in gamma-irradiated human umbilical vein endothelial cells (HUVECs). HUVECs were pretreated for 20 h with allicin (0.01-1 micro g/ml) and then exposed to 8 Gy radiation. Allicin significantly inhibited gamma IR-induced surface expression of ICAM-1 and ICAM mRNA in a dose-dependent manner. In addition, pretreatment with allicin resulted in the decrease of AP-1 activation and phosphorylation of the c-Jun NH2-terminal kinase (JNK) induced by gamma IR. These results suggest that allicin downregulates gamma IR-induced ICAM-1 expression via inhibition of both AP-1 activation and the JNK pathway and may be considered in therapeutic strategies for the management of patients treated with radiation therapy.

Cell Adhesion↗

PubMed2006

Jab1 mediates cytoplasmic localization and degradation of West Nile virus capsid protein.

The clinical manifestations of West Nile virus (WNV), a member of the Flavivirus family, include febrile illness, sporadic encephalitis, and paralysis. The capsid (Cp) of WNV is thought to participate in these processes by inducing apoptosis through mitochondrial dysfunction and activation of caspase-9 and caspase-3. To further identify the molecular mechanism of the WNV capsid protein (WNVCp), yeast two-hybrid assays were employed using WNV-Cp as bait. Jab1, the fifth subunit of the COP9 signalosome, was subsequently identified as a molecule that interacts with WNVCp. Immunoprecipitation and glutathione S-transferase pulldown assays confirmed that direct interaction could occur between WNVCp and Jab1. Immunofluorescence microscopy demonstrated that the overexpressed WNVCp, which localized to the nucleolus, was translocated to the cytoplasm upon its co-expression with Jab1. When treated with leptomycin B, Jab1-facilitated nuclear exclusion of WNVCp was prevented, which indicated that the CRM1 complex is required for Jab1-facilitated nuclear export of WNVCp. Moreover, Jab1 promoted the degradation of WNVCp in a proteasome-dependent way. Consistent with this, WNVCp-mediated cell cycle arrest at the G(2) phase in H1299 was prevented by exogenous Jab1. Finally, an analysis of WNVCp deletion mutants indicated that the first 15 amino acids were required for interaction with Jab1. Furthermore, the double-point mutant of the WNVCp, P5A/P8A, was incapable of binding to Jab1. These results indicate that Jab1 has a potential protective effect against pathogenic WNVCp and might provide a novel target site for the treatment of disease caused by WNV.

Active Transport, Cell Nucleus↗

PubMed2006

CML-1 inhibits TNF-alpha-induced NF-kappaB activation and adhesion molecule expression in endothelial cells through inhibition of IkBalpha kinase.

CML-1 is a purified extract from a mixture of 13 oriental herbs (Achyranthis Radix, Angelicae Gigantis Radix, Cinnamomi Cortex Spissus, Eucommiae Cortex, Glycyrrhizae Radix, Hoelen, Lycii Fructus, Paeoniae Radix, Rehmanniae Radix Preparata and Atractylodis Rhizoma, Zingiberis Rhizoma, Zizyphi Semen, Acori Graminei Rhizoma) that have been widely used for the treatment of inflammatory diseases in Asia. Since our previous study has been shown to have the anti-inflammatory activity of CML-1 in vivo and the upregulation of adhesion molecules in response to numerous inducing factors is associated with inflammation, this study examined the effect of CML-1 on the expression of adhesion molecules induced by TNF-alpha in cultured human umbilical vein endothelial cells (HUVECs). Preincubation of HUVECs for 20h with CML-1 (1-100mug/ml) dose-dependently inhibited TNF-alpha (10ng/ml)-induced adhesion of THP-1 monocytic cells, as well as mRNA and protein expression of E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). CML-1 was also shown to inhibit NK-kB activation induced by TNF-alpha. Furthermore, CML-1 inhibited TNF-alpha-induced IkB kinase activation, subsequent degradation of IkBalpha, and nuclear translocation of NK-kB. Evidence presented in this report demonstrated that CML-1 inhibited the adhesive capacity of HUVEC and the TNF-alpha-mediated induction of E-selectin, ICAM-1 and VCAM-1 in HUVEC by inhibiting the IkB/NF-kB signaling pathway at the level of IkB kinase, which may explain the ability of CML-1 to suppress inflammation and modulate the immune response.

Biotransformation↗

PubMed2006

Gamma-irradiation-induced intercellular adhesion molecule-1 (ICAM-1) expression is associated with catalase: activation of Ap-1 and JNK.

The ionizing radiation used in cancer therapy frequently produces damage to normal tissues and induces complex responses, including inflammation. The upregulation of the intercellular adhesion molecule-1 (ICAM-1) in response to numerous inducing factors is associated with inflammation. Therefore, this study examined the molecular mechanisms responsible for ICAM-1 expression induced by gamma-irradiation (gammaIR). ICAM-1 mRNA and cell surface expression were induced in A549 human lung epithelial cells after exposing them to gammaIR. Catalase expression and activity were also increased in gammaIR-treated cells. Treatment of the gammaIR-treated cells with catalase resulted in a significant increase in the ICAM-1 cell surface expression level. The catalase inhibitor 3-amino-1,2,4-triazole (AT) reduced the level of ICAM-1. Electrophoretic mobility shift assay (EMSA) analysis showed that activating protein 1 (AP-1) was activated by gammaIR, whereas NF-kappaB was not. Specific Jun N-terminal kinase (JNK) inhibition attenuated the upregulation of gammaIR stimulated ICAM-1. Western blot analysis revealed a marked elevation in activation of JNK. In addition, pretreatment with AT resulted in a decrease in the level of JNK phosphorylation and AP-1 activation. Overall, data suggest that induction of ICAM-1 expression by gammaIR is associated with catalase. Furthermore, catalase, JNKs, and AP-1 activation induce ICAM-1 upregulation through a sequential process.

Catalase↗

PubMed2005

Methamphetamine administration produces immunomodulation in mice.

The abuse of methamphetamine (MA) is an increasingly growing problem globally and produces serious side effects. In the present study, the immunomodulating effects of MA were examined on the immune system after MA (5 mg/kg body weight) was administered daily orally for 14 d. The immune system was evaluated by the antibody response to sheep red blood cells (SRBC; plaque assay and serum immunoglobulin [Ig] G), natural killer (NK) activity, lymphocyte subpopulations in the spleen and thymus, and concanavalin A (Con A)- and lipopolysaccharide (LPS)-stimulated lymphocyte proliferation using splenocytes. Body weight, spleen weight, and thymus weight generally decreased in MA-treated mice. MA treatment induced an increase in the percentage of CD4(+) cells with simultaneous decrease in the percentages of CD8(+) and double-positive CD4(+)CD8(+) in thymus. MA inhibited the IgM plaque-forming cell number, and lowered the level of IgG, the proliferation of mitogen-stimulated B and T cells, and the growth of granulocyte-macrophage colony-forming units (CFU-GM). Exposure to MA also decreased interleukin-2 production by splenocytes. In contrast, splenic NK activity in exposed mice was significantly enhanced. Taken together, data indicate that the immune system was suppressed by oral MA exposure.

Animals↗

PubMed2005

RETRACTED: Activation of murine peritoneal macrophages by sulfated exopolysaccharide from marine microalga Gyrodinium impudicum (strain KG03): involvement of the NF-kappa B and JNK pathway.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief, as there are concerns about inappropriate re-use of published figures. In this study, the same Western blot has been used to represent different studies with different drugs (methoxychalcone vs ganodermanondiol), cell extracts (macrophages versus hepatocytes) and different targets (Nrf2 vs LKB1). The concern was initially raised in PubPeer, the response from author on PubPeer was not acceptable. The journal Editor in Chief requested the author to provide the explanation, however, the author was not able to fulfil this request. PubPeer - Activation of murine peritoneal macrophages by sulfated exop… [pubpeer.com]

Animals↗

PubMed2005

Novel sulfated polysaccharide derived from red-tide microalga Gyrodinium impudicum strain KG03 with immunostimulating activity in vivo.

The high-sulfate-containing exopolysaccharide p-KG03 is produced by the red-tide microalga Gyrodinium impudicum strain KG03. The immunostimulatory effects of this sulfated exopolysaccharide were investigated by isolating peritoneal macrophages from mice 10 or 20 days after they had received a single dose of p-KG03 (100 or 200 mg/kg body weight). The cytotoxicity of the isolated macrophages for B16 tumor cells was tested, as B16 tumor cells are sensitive to tumor necrosis factor alpha (TNF-alpha) and nitric oxide. The activities of natural killer cells from the p-KG03-treated mice against YAC-1 mouse lymphoma cells were also tested. The nonspecific immune functions mediated by natural killer cells and macrophages were increased by treatment with p-KG03 in vivo. These results suggest that p-KG03 has immunostimulatory effects and enhances the tumoricidal activities of macrophages and NK cells in vivo. In addition, p-KG03 treatment increased the plaque-forming cell response to sheep red blood cells, as well as the levels of IgM and IgG Exposure to p-KG03 also increased the production by macrophages of cytokines, such as interleukins -1beta and -6, and TNF-alpha. This is the first report of a marine microalgal sulfated polysaccharide having immunostimulatory activities. The p-KG03 polysaccharide may be useful for the development of biotechnological and pharmaceutical products that incorporate bioactive marine exopolysaccharides.

Animals↗

PubMed2005

Immunomodulatory function of murine NK cell activity by alginate.

The in vivo immunomodulatory function of the activity of murine natural killer (NK) cells induced by high mannuronic acid-containing alginate (HMA) was examined. HMA was injected i.p at doses of 25 and 100 mg/kg. The NK activity was 3 times higher with 100 mg/kg HMA than the baseline. In addition, in vitro studies of splenocytes cultured with HMA for 20 h showed a significant increase in NK activity at E:T ratio of 100:1; a 160% and 210% increase at 10 and 100 microg/mL, respectively. There was a six fold increase in interferon-gamma production in a postculture of splenocytes with 100 microg/mL HMA. HMA had no suppressive effects on the lymphocyte function in the presence or absence of mitogens. This suggests that HMA is useful in cancer immunotherapy.

Alginates↗

PubMed2005

Anti-inflammatory activity of CML-1: an herbal formulation.

CML-1 is a purified extract from a mixture of 13 Oriental herbs (Achyranthis Radix, Angelicae Gigantis Radix, Cinnamomi Cortex Spissus, Eucommiae Cortex, Glycyrrhizae Radix, Hoelen, Lycii Fructus, Paeoniae Radix, Rehmanniae Radix Preparata and Atractylodis Rhizoma, Zingiberis Rhizoma, Zizyphi Semen, Acori Graminei Rhizoma) that have been widely used for the treatment of inflammatory diseases in Asia. The aim of this study was to investigate the anti-inflammatory and analgesic potential of CML-1. The animals used in this study were administered either vehicle or CML-1 (30, 100, 300 and 600 mg/kg) orally. The vascular permeability induced by acetic acid was significantly reduced by CML-1 in all doses. The swelling of the rat's hind paw induced by carrageenan was significantly inhibited by CML-1 in doses of 100, 300 and 600 mg/kg. In the case of rheumatoid arthritis induced by complete Freund's adjuvant in rats, the treatment with CML-1 at a dose level of 300 mg/kg inhibited edema. CML-1 at a dose level of 600 mg/kg inhibited acetic acid-induced writhing syndrome, however it did not have any anti-nociceptive action in the Randall-Selitto assay or the hot plate test. Our findings suggest that CML-1 has a potent anti-inflammatory activity.

Acetic Acid↗

PubMed2004

Caspase-independent cell death by allicin in human epithelial carcinoma cells: involvement of PKA.

Allicin, the major component of Garlic (Allium sativum) was examined for the ability to induce apoptosis and the mechanism of the induction of apoptosis in human epithelial carcinoma cells. Allicin inhibited cell growth and induced apoptosis in gastric epithelial cells. Treatment with allicin resulted in morphological changes, DNA fragmentation, hypodiploid DNA contents and the translocation of Bax to mitochondria. The release of cytochrome c from mitochondria into the cytosol, which is an initiator of the activation of caspase cascades, was observed in allicin-treated cells. However, pretreatment with Z-Val-Ala-Asp-fluoromethylketone (Z-VAD-fmk), a broad spectrum of caspase inhibitor, could not rescue apoptotic cells from allicin toxicity. Coincidently, caspase-3 activation and cleavage of PARP were not detected. In addition, caspase independent apoptosis-inducing factor (AIF) was released from mitochondria after treatment with allicin. After pre-incubation of cells with the protein kinase A (PKA) inhibitor H-89, allicin was not capable of inducing an increase of the rate of apoptosis with affecting the expression levels of Bax and AIF. These data demonstrate that allicin induces a caspase-independent apoptotic pathway mediated by mitochondrial release of AIF and PKA appears to be involved in allicin-induced apoptosis in gastric epithelial cells.

Apoptosis↗

PubMed2004

Modulation of murine macrophage function by methamphetamine.

The abuse of methamphetamine (MA) is an increasingly growing problem globally and produces serious side effects. In the present study, the immunomodulating effects of MA were examined on murine peritoneal macrophages after MA (5 mg/kg body weight) was administered daily orally for 2 wk. When purified macrophages were stimulated with lipopolysaccharide (LPS), the tumoricidal activity induced by LPS was significantly suppressed by MA. MA also inhibited poly I:C-induced antiviral activity in macrophages and decreased the number of peritoneal macrophages. FACS analysis showed that the expression of CD14 was markedly decreased by MA in LPS-stimulated macrophages. The production of nitric oxide (NO) and tumor necrosis factor (TNF)-alpha: which are known to be major effector molecules in macrophage-mediated cytotoxicity, was decreased by MA. MA produced a significant effect on phagocytosis and interleukin-1 (IL-1) and IL-6 at 14 d. In addition, the level of hydrogen peroxide (H2O2) was not altered by MA. Taken together, these data indicate that MA has a differential immunomodulating effect on macrophage secretory and cellular activities.

Animals↗

PubMed2004

Vitamin C blocks TNF-alpha-induced NF-kappaB activation and ICAM-1 expression in human neuroblastoma cells.

Interactions of the cell adhesion molecules are known to play important roles in mediating inflammation. The proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), activates the NF-kappaB signaling pathway, which induces the expression of various genes, such as intercellular adhesion molecule-1 (ICAM-1). In this study, the effect of vitamin C on the ICAM-1 expression induced by TNF-alpha in a human neuroblastoma cell line, SK-N-SH was investigated. Treatment with vitamin C resulted in the downregulation of the TNF-alpha-induced surface expression and ICAM-1 mRNA levels in a concentration-dependent manner. Moreover, a gel shift analysis indicated that vitamin C dose-dependently inhibited the NF-kappaB activation and IkappaBalpha degradation induced by TNF-alpha. Taken together, these results suggest that vitamin C downregulates TNF-alpha-induced ICAM-1 expression via the inhibition of NF-kappaB activation.

Antioxidants↗

PubMed2003

Immune alterations in mice exposed to the herbicide simazine.

Simazine, a triazine herbicide, was investigated for its in vivo immunomodulatory properties. Male C57Bl/6 mice were treated with vehicle or 300 or 600 mg/kg body weight (bw) simazine daily orally for 4 wk. The immune system was evaluated by the antibody response to sheep red blood cells (SRBC; plaque assay and serum immunoglobulin G), natural killer (NK) and macro-phage activities, lymphocyte subpopulations in the spleen and thymus, and concanavalin A (Con A)- and lipopolysaccharide (LPS)-stimulated lymphocyte proliferation using splenocytes. Body weight and spleen and thymus weight decreased generally in simazine-treated mice, while the weight of adrenal glands was higher than in the control. Simazine treatment (600 mg/kg) induced an increase in the percentage of CD4(+) cells in spleen and CD8 + in thymus. Simazine inhibited the IgM plaque-forming cell numbers and lowered the level of IgG and the proliferation of mitogen-stimulated B cells and T cells. In addition, splenic NK and peritoneal macrophage activities in exposed mice were significantly decreased. Exposure to simazine also decreased cytokine production by macrophages, such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-alpha). Taken together, data indicate that the immune system was suppressed by oral simazine exposure.

Administration, Oral↗

PubMed2003

Reversal of P-glycoprotein-mediated multidrug resistance by ginsenoside Rg(3).

Multidrug resistance has been a major problem in cancer chemotherapy. In this study, in vitro and in vivo modulations of MDR by ginsenoside Rg(3), a red ginseng saponin, were investigated. In flow cytometric analysis using rhodamine 123 as an artificial substrate, Rg(3) promoted accumulation of rhodamine 123 in drug-resistant KBV20C cells in a dose-dependent manner, but it had no effect on parental KB cells. Additionally Rg(3) inhibited [3H]vinblastine efflux and reversed MDR to doxorubicin, COL, VCR, and VP-16 in KBV20C cells. Reverse transcriptase-polymerase chain reaction and immuno-blot analysis after exposure of KBV20C cells to Rg(3) showed that inhibition of drug efflux by Rg(3) was due to neither repression of MDR1 gene expression nor Pgp level. Photo-affinity labeling study with [3H]azidopine, however, revealed that Rg(3) competed with [3H]azidopine for binding to the Pgp demonstrating that Rg(3) competed with anticancer drug for binding to Pgp thereby blocking drug efflux. Furthermore, Rg(3) increased life span in mice implanted with DOX-resistant murine leukemia P388 cells in vivo and inhibited body weight increase significantly.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

Modulation of TNF-alpha-induced ICAM-1 expression, NO and H2O2 production by alginate, allicin and ascorbic acid in human endothelial cells.

Plant nutrients are believed to provide protection against various diseases including inflammation. Since interactions of the cell adhesion molecules are known to play important roles in mediating inflammation, inhibiting adhesion protein upregulation is a possible therapeutic target. In this study, the interacellular adhesion molecule-1 (ICAM-1) was induced in human umbilical endothelial cells (HUVECs) after stimulation with TNF-alpha. In addition, alginate, ascorbic acid and allicin were demonstrated to inhibit the TNF-alpha induced expression of ICAM-1 on the HUVECs in a dose-dependent manner. These compounds also inhibited the production of NO and H2O2 induced by TNF-alpha, which suggests that the inhibition of ICAM-1 expression by the three compounds may be due to the modulated production of the reactive oxygen/nitrogen components. Overall, these results indicate that these dietary components have a therapeutic potential in the treatment of various inflammatory disorders associated with an increase in endothelial leukocyte adhesion molecules.

Alginates↗

PubMed2003

Antiviral and tumoricidal activities of alginate-stimulated macrophages are mediated by different mechanisms.

Macrophages play an important role in host defenses by killing tumors and virus infections and producing secretory products. High mannuronic acid (HMA) containing alginate was examined to determine the mechanisms by which HMA-activated macrophages resist infection with HSV-1 and inhibit the growth of tumor cells. The ability of macrophages to resist infection with HSV-1 or to inhibit the growth of tumor cells was assessed following treatment with HMA alginate in the presence of either antibodies to various cytokines or inhibitors/scavengers of toxic macrophage products. Only antibodies to IFN-alpha/beta were able to abrogate the protective effects of HMA alginate in macrophages infected with HSV-1, suggesting that the antiviral activity induced by this immunomodulator was mediated by the production of IFN-beta. In contrast, anti-TNF-alpha, anti-IFN and inhibitors of nitric oxide and reactive oxygen species were all able to partially abrogate HMA-induced cytostatic activity, suggesting that multiple mechanisms are involved in macrophage cytostasis. These results indicate that the HMA-induced intrinsic antiviral and extrinsic cytotoxic activites are mediated by different mechanisms.

Alginates↗

PubMed2003

Induction of apoptosis and expression of apoptosis related genes in human epithelial carcinoma cells by Helicobacter pylori VacA toxin.

Virulence factors produced by Helicobacter pylori have been known to be associated with serious gastroduodenal diseases. The aims of this study were to clarify the apoptosis-inducing properties of vacuolating cytotoxin (VacA) and examine the expression of apoptosis related proteins in human epithelial carcinoma cells expressing (AGS) or lacking (Kato III) p53. The midregion VacA homolog from H. pylori strain Q35 (Korean isolate) was cloned, expressed and sequenced. Recombinant VacA (VacA(418-799)) inhibited cell growth and induced apoptosis in gastric epithelial cells. Treatment with VacA(418-799) resulted in morphological changes and DNA fragmentation. Cell cycle analysis revealed subdiploid cells suggesting apoptosis, which was confirmed by the activation of caspase-3 and cleavage of PARP. VacA(418-799) also mediated a prolongation of the cell cycle progression in G1 phase. Furthermore, VacA(418-799) increased the expression of p53, p21(waf1/cip1) and Bax in AGS cells, but not in Kato III cells and did not affect the phosphorylation of Rb in both cell lines. These results indicate that recombinant VacA of H. pylori induces apoptosis in both Kato III and AGS cells, regardless of p53 status and suggest that VacA(418-799) mediate the development of gastric diseases through cell cycle arrest in the G1 phase. VacA(418-799) induction of apoptosis is associated with up-regulation of p53, p21(waf1/cip1), Bax in AGS cells and activation of caspase-3 in both cell lines.

Amino Acid Sequence↗