• Title/Summary/Keyword: $\kappa$

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Silymarin Inhibits Morphological Changes in LPS-Stimulated Macrophages by Blocking NF-${\kappa}B$ Pathway

  • Kim, Eun Jeong;Lee, Min Young;Jeon, Young Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.3
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    • pp.211-218
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    • 2015
  • The present study showed that silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), inhibited lipopolysaccharide (LPS)-induced morphological changes in the mouse RAW264.7 macrophage cell line. We also showed that silymarin inhibited the nuclear translocation and transactivation activities of nuclear factor-kappa B (NF-${\kappa}B$), which is important for macrophage activation-associated changes in cell morphology and gene expression of inflammatory cytokines. BAY-11-7085, an NF-${\kappa}B$ inhibitor, abrogated LPS-induced morphological changes and NO production, similar to silymarin. Treatment of RAW264.7 cells with silymarin also inhibited LPS-stimulated activation of mitogen-activated protein kinases (MAPKs). Collectively, these experiments demonstrated that silymarin inhibited LPS-induced morphological changes in the RAW264.7 mouse macrophage cell line. Our findings indicated that the most likely mechanism underlying this biological effect involved inhibition of the MAPK pathway and NF-${\kappa}B$ activity. Inhibition of these activities by silymarin is a potentially useful strategy for the treatment of inflammation because of the critical roles played by MAPK and NF-${\kappa}B$ in mediating inflammatory responses in macrophages.

Tumor Necrosis Factor-Alpha $(TNF-{\alpha})$ Induces PTEN Expression in HL-60 Cells (백혈병세포에서 종양괴사인자에 의한 PTEN 발현증가)

  • Lee Seung-Ho;Park Chul-Hong;Kim Byeong-Su
    • Journal of Food Hygiene and Safety
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    • v.21 no.3
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    • pp.181-188
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    • 2006
  • Tumor necrosis factor-alpha $(TNF-{\alpha})$ plays a variety of biological functions such as apoptosis, inflammation and immunity. PTEN also has various cellular function including cell growth, proliferation, migration and differentiation. Thus, possible relationships between two molecules are suggested. $(TNF-{\alpha})$has been known to downregulate PTEN via nuclear factor-kappa $B(NF-{\kappa}B)$ pathway in the human colon cell line, HT-29. However, here we show the opposite finding that $(TNF-{\alpha})$ upregulates PTEN via activation of $NF-{\kappa}B$ in HL-60 cells. $TNF-{\alpha}$ increased PTEN expression at HL-60 cells in a time- and dose-dependent manner, but the response was abolished by disruption of $NF-{\kappa}B$ with p65 anisense oligonucleotide or pyrrolidine dithiocarbamate (PDTC). We found that $TNF-{\alpha}$ activated the $NF-{\kappa}B$ pathways, evidenced by the translocation of p65 to the nucleus in $TNF-{\alpha}-treated$ cells. We conclude that $TNF-{\alpha}$ induces upregulation of PTEN expression through $NF-{\kappa}B$ activation in HL-60 cells.

Pycnogenol, a Standardized Extract of French Maritime Pine Bark, Inhibited the Transcriptional Expression of Th2 Cytokines by Suppressing $NF-{\kappa}B$ Activation in Primary Splenocytes of C57BL/6 Mice with Murine AIDS (Murine AIDS 감염쥐 splenocytes에서 $NF-{\kappa}B$의 활성화 억제를 통한 pycnogenol의 Th2 cytokines의 mRNA 발현 조절 효과)

  • Lee, Jeong-Min
    • Korean Journal of Food Science and Technology
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    • v.38 no.6
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    • pp.829-834
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    • 2006
  • LP-BM5 murine leukemia retrovirus induces the immune dysfunction by imbalanced secretion of Th1 and Th2 cytokines in the murine AIDS model. In the present study, it was investigated whether pycnogenol (Pyc) administration could deactivate $NF-{\kappa}B$ to regulate the gene expression of Th1 and Th2 cytokines in C57BL/6 mice with murine AIDS. Treatment with Pyc for 12 weeks significantly inhibited the loss of body weight and enlargement of spleen and lymph node usually seen with AIDS. Moreover, Pyc increased the plasma level of Th1 cytokines, IL-2 and $IFN-{\gamma}$, while reducing the plasma level of Th2 cytokines, IL-6, IL-10, and $TNF-{\alpha}$. In primary culture of splenocytes, mRNA expression of Th2 cytokines was suppressed, but that of Th1 cytokines was not affected. The LP-BM5 retrovirus infection stimulated the cytoplasmic activation of $NF-{\kappa}B$ and nuclear translocation of $I-{\kappa}B$, whereas Pyc administration significantly reduced $NF-{\kappa}B$ activation and $I-{\kappa}B$ degradation. These results suggested that the inhibitory effect of Pyc on Th2 cytokines in mice with murine AIDS was dependent on suppression of the $NF-{\kappa}B$ signaling pathway and was not dependent on $INF-{\gamma}$ level, which regulates Th2 cytokines.

Effect of trans-10, cis-12 Conjugated Linoleic Acid on Calcium-Dependent Reactive Oxygen Species and Nitric Oxide Production and Nuclear Factor-${\kappa}B$ Activation in Lipopolysaccharide-Stimulated RAW 264.7 Cells (LPS 자극 RAW 264.7 세포에 있어서 칼슘의존성 ROS와 NO 생산 및 NF-${\kappa}B$ 활성에 대한 CLA의 억제효과)

  • Choi, Tae-Won;Kang, Byeong-Teck;Kang, Ji-Houn;Yang, Mhan-Pyo
    • Journal of Veterinary Clinics
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    • v.32 no.2
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    • pp.135-140
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    • 2015
  • Trans-10, cis-12-conjugated linoleic acid (t10c12-CLA) has been shown to participate in the regulation of anti-inflammatory effects. The objectives of this study were to examine the effects of t10c12-CLA on reactive oxygen species (ROS) and nitric oxide (NO) production and nuclear factor-kappaB (NF-${\kappa}B$) activation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and to determine whether these effects were associated with change of intracellular calcium ion ($Ca^{2+}$). ROS production was increased in LPS-stimulated RAW 264.7 cells, and this effect was suppressed by 1,2-bis-(o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM), a calcium chelator. t10c12-CLA suppressed ROS production in LPS-stimulated RAW 264.7 cells, which was further more decreased by treatment with BAPTA/AM. These indicated that t10c12-CLA decreases $Ca^{2+}$-dependent ROS production in LPS-stimulated RAW 264.7 cells. Similarly, NF-${\kappa}B$ p65 DNA binding activity and NO production were decreased by treatment with either t10c12-CLA, BAPTA/AM, or t10c12-CLA and BAPTA/AM combination. However, there were no differences between t10c12-CLA and BAPTA/AM treatment in NO production of LPS-stimulated RAW 264.7 cells. These data indicate that t10c12-CLA inhibits the increases in ROS and NO production and the NF-${\kappa}B$ activation in LPS-stimulated condition. These results suggested that CLA exerts potent anti-inflammatory effects by suppression of LPS-induced ROS and NO production, and NF-${\kappa}B$ activationn via $Ca^{2+}$-dependent pathway.

Relationship of Inhibitory Effects of Dichroa febrifuga and $IKK{\gamma}$ on the Activation of $NF-{\kappa}B$ (상산의 $NF-{\kappa}B$ 활성억제작용과 $IKK{\gamma}$의 연관성 연구)

  • Choi, Byung-Tae;Lee, Yong-Tae;Hwang, Jang-Sun;Moon, Hae-In;Lee, Kyung-Soo;An, Won-Gun;Kim, Dong-Wan
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.3
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    • pp.651-656
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    • 2006
  • Activation of $NF-{\kappa}B$ is known to be a trigger of various cellular disorders including inflammatory and autoimmune diseases such as rheumatoid arthritis. Numerous approaches are ongoing within laboratories to identify potential therapeutic agents which inhibit the $NF-{\kappa}B$ activation. In this study, we have tested the inhibitory effects of five traditional medicines on the activation of $NF-{\kappa}B$ by NIK. Among three medicines which exhibited inhibitory effect on the expression of $NF-{\kappa}B$ repoter plasmid, we investigated further the inhibitory mechanism of Dichroa febrifuga in connection with IKKY activity. Wild type $IKK{\gamma}$ inhibited the $NF-{\kappa}B$ activation by NIK but the C-terminal deletion mutant of IKKY did not show the inhibitory effect, indicating that the C-terminal leucine zipper domain of $NF-{\kappa}B$ is important for the inhibition of $NF-{\kappa}B$ activation. The water extract of Dichroa febrifuga(DFE) also strongly inhibited the $NF-{\kappa}B$ activation by NIK. The inhibitory activity of DFE appeared to be independent of the expression of $IKK{\gamma}$, suggesting that the pathways of inhibition by Dichroa febrifuga and $IKK{\gamma}$ are different. Our results suggest that Dichroa febrifuga can be used as a medicine for inhibition of the $NF-{\kappa}B$ activation in a wide range of cells without relation to the expression of $IKK{\gamma}$.

Concept of Rock Physics Modeling and Application to Donghae-1 Gas Field (암석물리모델링의 개념과 동해-1 가스전에의 적용)

  • Hu, Doc-Ki;Keehm, Young-Seuk
    • 한국지구물리탐사학회:학술대회논문집
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    • 2008.10a
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    • pp.173-178
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    • 2008
  • In this paper, we will introduce rock physics modeling technique, which interrelate reservoir properties with seismic properties, and apply the technique to the Donghae-1 gas reservoir. From well-log data analysis, we obtained velocityporosity (Vp-$\phi$) relations for each formation. These relations can used to predict porosity from seismic data. In addition, we analyzed permeability data, which were obtained from core measurements and computational rock physics simulations. We then obtained permeability-porosity ($\kappa-\phi$) relations. Combining $\kappa-\phi$ with Vp-$\phi$ relations, we finally present quantitative Vp-$\kappa$ relations. As to Vp-$\phi$ modeling, we found that the degree of diagenesis and clay contents increase with depth. As to Vp-$\kappa$ relations, though \kappa-\phi relations are almost identical for all formations, we could obtain distinct Vp-$\kappa$ relations due to Vp-$\phi$ variations. In conclusion, the rock physics modeling, which bridges between seismic properties and reservoir properties, can be a very robust tool for quantitative reservoir characterization with less uncertainty.

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Induction of Apoptosis by HDAC Inhibitor Trichostatin A through Activation of Caspases and NF-κB in Human Prostate Epithelial Cells. (인체 전립선 상피세포에서 HDAC 저해제 trichostatin A의 caspase 및 NF-κB의 활성화를 통한 apoptosis 유도)

  • Park, Cheol;Jin, Cheng-Yun;Choi, Byung-Tae;Lee, Won-Ho;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.18 no.3
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    • pp.336-343
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    • 2008
  • Histone deacetylases (HDACs) inhibitors have emerged as the accessory therapeutic agents for various human cancers, since they can block the activity of specific HDACs, restore the expression of some tumor suppressor genes and induce cell differentiation, cell cycle arrest and apoptosis in vitro and in vivo. In the present study, we investigated that the effect of trichostatin A (TSA), an HDAC inhibitor, on the cell growth and apoptosis, and its effect on the nuclear factor-kappaB $(NF-{\kappa}B)$ activity in 267B1 human prostate epithelial cells. Exposure of 267B1 cells to TSA resulted in growth inhibition and apoptosis induction in and dose-dependent manners as measured by fluorescence microscopy, agarose gel electrophoresis and flow cytometry analysis. TSA treatment inhibited the levels of IAP family members such as c-IAP-1 and c-IAP-2 and induced the proteolytic activation of caspase-3, -8 and -9, which were associated with concomitant degradation of poly (ADP-ribose)-polymerase, ${\beta}-catenin$ and laminin B proteins. The increase in apoptosis by TSA was connected with the translocation of $NF-{\kappa}B$ from cytosol to nucleus, increase of the DNA binding as well as promoter activity of $NF-{\kappa}B$, and degradation of cytosolic inhibitor of KappaB $(I{\kappa}B)-{\alpha}$ protein. We therefore concluded that TSA demonstrated anti-proliferative and apoptosis-inducing effects on 267B1 cells in vitro, and that the activation of caspases and $NF-{\kappa}B$ may play important roles in its mechanism of action. Although further studies are needed, these findings provided important insights into the possible molecular mechanisms of the anti-cancer activity of TSA.

The Anti-Inflammatory Effects of Persicaria thunbergii Extracts on Lipopolysaccharide-Stimulated RAW264.7 Cells (Lipopolysaccharide로 처리 된 RAW264.7 세포에서 고마리 추출물의 항염증 효과)

  • Kim, Sang-Bo;Seong, Yeong-Ae;Jang, Hee-Jae;Kim, Gun-Do
    • Journal of Life Science
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    • v.21 no.12
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    • pp.1689-1697
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    • 2011
  • In this study, we investigated the anti-inflammation effect of Persicaria thunbergii (P. thunbergii) on RAW 264.7 murine macrophage cells. The anti-inflammatory activity of P. thunbergii was determined by measuring expression of the LPS-induced inflammatory proteins, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and nuclear factor-${\kappa}B$ (NF-${\kappa}B$), and the production of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$). Methanol extract of P. thunbergii decreased the expression of iNOS, COX-2 and NF-${\kappa}B$, and increased the expression of HO-1 in LPS-stimulated RAW264.7 cells. Methanol extract was fractioned by n-butanol, hexane and ethyl acetate (EtOAc) and each fraction was tested for inhibitory effects on inflammation. Among the sequential solvent fractions, the EtOAc soluble fraction was investigated by the expression of prostaglandin $E_2$ ($PGE_2$), and showed decreasing form to the dose-dependent manner. EtOAc extract showed the most effective inhibitory activity of the expression of iNOS, COX-2 and NF-${\kappa}B$, and the production of NO. The study showed that P. thunbergii has anti-inflammatory activity through the decrease of NO and inhibition of iNOS, COX-2, $PGE_2$ and NF-${\kappa}B$ expression, and by the increase of HO-1 enzyme. This study needs for more investigation to find out the most effective single compound with anti-inflammatory activity.

A SHORT NOTE ON BIHARMONIC SUBMANIFOLDS IN 3-DIMENSIONAL GENERALIZED (𝜅, 𝜇)-MANIFOLDS

  • Sasahara, Toru
    • Bulletin of the Korean Mathematical Society
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    • v.53 no.3
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    • pp.723-732
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    • 2016
  • We characterize proper biharmonic anti-invariant surfaces in 3-dimensional generalized (${\kappa}$, ${\mu}$)-manifolds with constant mean curvature by means of the scalar curvature of the ambient space and the mean curvature. In addition, we give a method for constructing infinity many examples of proper biharmonic submanifolds in a certain 3-dimensional generalized (${\kappa}$, ${\mu}$)-manifold. Moreover, we determine 3-dimensional generalized (${\kappa}$, ${\mu}$)-manifolds which admit a certain kind of proper biharmonic foliation.