• Title/Summary/Keyword: Nuclear factor-kappa

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2-O-digalloyl-1,3,4,6-tetra-O-galloyl-β-D-glucose isolated from Galla Rhois suppresses osteoclast differentiation and function by inhibiting NF-κB signaling

  • Ihn, Hye Jung;Kim, Tae Hoon;Kim, Kiryeong;Kim, Gi-Young;Jeon, You-Jin;Choi, Yung Hyun;Bae, Jong-Sup;Kim, Jung-Eun;Park, Eui Kyun
    • BMB Reports
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    • v.52 no.6
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    • pp.409-414
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    • 2019
  • Natural compounds isolated from medicinal herbs and plants have immense significance in maintaining bone health. Hydrolysable tannins have been shown to possess a variety of medicinal properties including antiviral, anticancer, and anti-osteoclastogenic activities. As a part of a study on the discovery of alternative agent against skeletal diseases, we isolated a hydrolysable tannin, 2-O-digalloyl-1,3,4,6-tetra-O-galloyl-${\beta}$-D-glucose (DTOGG), from Galla Rhois and examined the effect on osteoclast formation and function. We found that DTOGG significantly inhibited receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation by downregulating the expression of the key regulator in osteoclastogenesis as well as osteoclast-related genes. Analysis of RANKL/RANK signaling revealed that DTOGG impaired activation of $I{\kappa}B{\alpha}$ and p65 in the nuclear factor kappa-lightchain-enhancer of activated B cells (NF-${\kappa}B$) signaling pathway. Furthermore, DTOGG reduced bone resorbing activity of osteoclasts, compared to the vehicle-treated control. These results suggest that DTOGG could be a useful natural compound to manage osteoclast-mediated skeletal diseases.

Expression of Nuclear Factor Kappa B (NF-κB) as a Predictor of Poor Pathologic Response to Chemotherapy in Patients with Locally Advanced Breast Cancer

  • Prajoko, Yan Wisnu;Aryandono, Teguh
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.595-598
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    • 2014
  • Background: NF-${\kappa}B$ inhibits apoptosis through induction of antiapoptotic proteins and suppression of proapoptotic genes. Various chemotherapy agents induce NF-${\kappa}B$ translocation and target gene activation. We conducted the present study to assess the predictive value of NF-${\kappa}B$ regarding pathologic responses after receiving neoadjuvant chemotherapy. Materials and Methods: We enrolled 131 patients with locally advanced invasive ductal breast carcinoma. Immunohistochemistry (IHC) was used to detect NF-${\kappa}B$ expression. Evaluation of pathologic response was elaborated with the Ribero classification. Results: Expression of NF-${\kappa}B$ was significantly associated with poor pathological response (p=0.02). From the multivariate analysis, it was found that the positive expression of NF-${\kappa}B$ yielded RR=1.74 (95%CI 0.77 to 3.94). Conclusions: NF-${\kappa}B$ can be used as a predictor of poor pathological response after neoadjuvant chemotherapy.

Triptolide Inhibits Lipopolysaccharide-Induced MUC5AC/5B Expression via Nuclear Factor-Kappa B in Human Airway Epithelial Cells (사람 호흡기 상피세포에서 Triptolide의 Nuclear Factor-Kappa B를 통한 Lipopolysaccharide로 유도된 MUC5AC/5B 발현 억제 효과)

  • Seo, Bo Hyeon;Choi, Tae Yeong;Choi, Yoon Seok;Bae, Chang Hoon;Na, Hyung Gyun;Song, Si-Youn;Kim, Yong-Dae
    • Korean Journal of Otorhinolaryngology-Head and Neck Surgery
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    • v.61 no.12
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    • pp.674-680
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    • 2018
  • Background and Objectives The representative mucin genes in the human airway are MUC5AC and MUC5B, which are regulated by several inflammatory and anti-inflammatory substances. Triptolide (TPL), udenafil, betulinic acid, changkil saponin, and glucosteroid are some of the many anti-inflammatory substances that exist. TPL is a diterpenoid compound from the thunder god vine, which is used in traditional Chinese medicine for treatment of immune inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, nephritis and asthma. However, the effects of TPL on mucin expression of human airway epithelial cells have yet to be reported. Hence, this study investigated the effect of TPL on lipopolysaccharide (LPS)-induced MUC5AC and MUC5B expression in human airway epithelial cells. Subjects and Method The NCI-H292 cells and the primary cultures of human nasal epithelial cells were used to investigate the effects of TPL on LPS-induced MUC5AC and MUC5B expression using real-time polymerase chain reaction, enzyme immunoassay, and Western blot. Results TPL significantly decreased the LPS-induced MUC5AC and MUC5B mRNA expression and protein production. TPL also significantly decreased the nuclear factor-kappa B (NF-kB) phosphorylation. Conclusion These results suggest that TPL down regulates MUC5AC and MUC5B expression via inhibition of NF-kB activation in human airway epithelial cells. This study may provide important information about the biological role of triptolide on mucus-secretion in airway inflammatory diseases and the development of novel therapeutic agents for controlling such diseases.

The effect of Gagamchunggan-tang on lipopolysaccharide-induced expression of $NF{\kappa}-B$ downstream genes in HepG2 cell (Lipopolysaccharide로 유발된 HepG2 세포의 염증반응에 대한 가감청간탕의 효과에 대한 연구)

  • Kim Sung-Hwan;Seo Sang-Ho;Hong Sang-Hoon
    • The Journal of Internal Korean Medicine
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    • v.24 no.1
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    • pp.113-122
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    • 2003
  • Objective : The aim of this study was to evaluate the efficacy of Gagamchunggan-tang on anti-inflammation reaction with lipopolysaccharide (LPS)-induced HepG2 cell. Method : We examined the effects of the Gagamchunggan-tang, a traditional drug for liver inflammation, on the process of lipopolysaccharide(LPS)-induced nuclear factor-${\kappa}Bp65(NF-{\kappa}Bp65)$ activation in HepG2 cell. SDS-PAGE, Western blotting, Immunofluorescence staining were studied. Results : Immunoblot analysis showed that the level of nucleic $NF-{\kappa}Bp65$ was rapidly up-regulated and cytosolic inhibitory $I-{\kappa}B{\alpha}$ was down-regulated by LPS challenge. While Gagamchunggan-tang inhibited an increase of $NF-{\kappa}Bp65$ and degradation of $I-{\kappa}B{\alpha}$ in HepG2 cell. Besides LPS-induced expression of a group of genes, such as tumor necrosis factor-${\alpha}(TNF-{\alpha})$, inducible nitric oxide synthase(iNOS) and cyclooxygenase-2 (COX-2), are repressed by Gagamchunggan-tang. It may be concluded that Gagamchunggan-tang attenuates the progress of LPS-induced inflammation by reduction of $NF-{\kappa}Bp65$ activation. Conclusion : The Gagamchunggan-tang would be useful as a therapeutic agent for endotoxin-induced liver disease.

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Experimental Study about Pathway of Aconiti Ciliare Tuber on Allergic Reaction of Inflammation (초오의 항알레르기 염증반응 및 기전탐색에 관한 연구)

  • Kim, Won-Ill
    • Korean Journal of Oriental Medicine
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    • v.16 no.3
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    • pp.155-166
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    • 2010
  • Objetives : The purpose of this study was to examine the pathway of anti-allergic effects of Aconiti Ciliare Tuber (ACT). Methods : We examined cell viability, ${\beta}$-hexosaminidase release, pro-inflammatory cytokines secretion and mRNA expressions, nuclear factor-kappa B (NF-${\kappa}B$) (p65) activation, inhibitor kappa B-alpha ($I{\kappa}B-{\alpha}$) degradation, and MAPKs activation from RBL-2H3 cells pre-treatment by ACT of 1.0 mg/ml, 2.0 mg/ml separately. Results : We observed that ACT reduced the secretion of ${\beta}$-hexosaminidase, TNF-${\alpha}$, IL-4 and the expression of COX-2 mRNA in RBL-2H3 cells. Futhermore, ACT inhibited the levels of activation of NF-${\kappa}B$ (p65) protein, ERK MAPK, and degradation of $I{\kappa}B-{\alpha}$ in RBL-2H3 cells. Conclusions : These results show that ACT has an anti-histamine effect and inhibitory effect of NF-${\kappa}B$ (p65) through regulation of $I{\kappa}B-{\alpha}$ degradation. This improves that ACT could be used as an anti-allergic medicine.

Experimental Study about the Pathway of Inflammatory Allergic Reaction of Cheonmaec-tang (천맥탕(天麥湯)의 알레르기 염증반응 및 기전탐색에 관한 연구)

  • Kim, Yong-Hyeon;Lee, Seung-Yeon;Kim, Won-Il
    • The Journal of Pediatrics of Korean Medicine
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    • v.24 no.1
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    • pp.93-103
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    • 2010
  • Objectives The purpose of this study was to examine the pathway of anti-allergic effects of Cheonmaec-tang (CMT). Methods We examined the cell viability, $\beta$-hexosaminidase release, pro-inflammatory cytokines secretion and mRNA expressions, nuclear factor-kappa B (NF-${\kappa}B$) (p65) activation, inbibitor kappa B-alpha ($I{\kappa}B-{\alpha}$) degradation, and MAPKs activation in RBL-2H3 cells pre-treated by CMT of 2.0 mg/ml, 4.0 mg/ml separately. Results We observed that CMT reduced the secretion of $\beta$-hexosaminidase, TNF-$\alpha$, IL-4 and the expression of COX-2 mRNA in RBL-2H3 cells. Furthermore, CMT inhibited the levels of activation of NF-${\kappa}B$ (p65) protein, ERK MAPK, and degradation of $I{\kappa}B-{\alpha}$ in RBL-2H3 cells. Conclusions These results show that CMT has an anti-histamine effect and inhibitory effect of NF-${\kappa}B$ (p65) through regulation of $I{\kappa}B-{\alpha}$ degradation. These suggest that CMT could be used as an anti-allergic medicine.

Anti-inflammatory Effects of Abeliophyllum distichum Flower Extract and Associated MAPKs and NF-κB Pathway in Raw264.7 Cells

  • Lee, Jin-Wook;Kang, Yoon-Joong
    • Korean Journal of Plant Resources
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    • v.31 no.3
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    • pp.202-210
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    • 2018
  • Abeliophyllum distichum is a medicinal plant used in regional traditional medicine to relieve pain in inflammatory processes. In this study, anti-inflammatory effects of Abeliophyllum distichum flower (ADF) extract were examined. Furthermore, possible molecular mechanisms of the anti-inflammatory effects were dissected. The anti-inflammatory activity was investigated by inhibition of lipopolysaccharide (LPS) induced pro-inflammatory cytokine production in murine macrophage-like cell line Raw264.7 cells. The measurement of the induced pro-inflammatory cytokine levels were carried out by ELISA. The phosphorylation of ERK1/2, JNK, and MAPK, and the nuclear expression of nuclear factor NF-${\kappa}B$ p65 were investigated by Western blot analysis. The extract of ADF significantly decreased the production of pro-inflammatory cytokines. In addition, the extract suppressed the phosphorylation of ERK1/2, JNK, and p38 MAPK, and the nuclear translocation of NF-${\kappa}B$ p65 in activated cells. Our findings provide evidence for the popular use of Abeliophylli distichum in inflammation around Goesan region and also suggest that the flower extract has potential therapeutic benefits against various inflammatory diseases.