• Food Science and Biotechnology
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• 제14권1호
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• pp.94-98
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• 2005

Bone resorption surrounding tooth root causes tooth loss in periodontitis patients. Osteoclast has bone resorption activity. Effects of Artemisia asiatica on bone resorption induced by periodontopathogens, Porphyromonas gingivalis and Treponema denticola, were examined using co-culture systems of mouse osteoblasts and bone marrow cells. Addition of A. asiatica ethanol extract to bacterial sonicate abolished bacteria-induced osteoclastogenesis. To determine inhibitory mechanism of A. asiatica against osteoclastogenesis, effects of A. asiatica on expressions of osteoclastogenesis-inducing factors such as receptor activator of NF-${\kappa}B$ ligand (RANKL), prostaglandin $E_2\;(PGE_2)$, interleukin (IL)-1, and tumor necrosis factor (TNF)-${\alpha}$, in osteoblasts were examined. A. asiatica suppressed expressions of RANKL, $PGE_2$, IL-$1{\beta}$, and TNF-${\alpha}$ increased by each bacterial sonicate. These results suggest inhibitory action of A. asiatica against osteoclastogenesis is associated with down-regulations of RANKL, $PGE_2$ IL-$1{\beta}$, and TNF-${\alpha}$ expressions.

• Bulletin of the Korean Chemical Society
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• 제34권4호
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• pp.1089-1095
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• 2013

The tumor necrosis factor-receptor 1 (TNFR1)-associated death domain protein (TRADD) contains an N-terminal TRAF binding domain and a C-terminal death domain. TRADD is known to interact directly with TNF receptor 2 (TNFR2) and the Fas-associated death domain protein (FADD), which are signal transducers that activate NF-${\kappa}B$ and induce apoptosis, respectively. To date, there has been no structural information on the TRADD and FADD death domain (DDs) complex. In this study, the death domains of TRADD and FADD were co-expressed and purified from Escherichia coli for structural characterization. We found that human TRADD (hTRADD) interacted strongly with mouse FADD (mFADD) via their DDs and interacted weakly with human FADD (hFADD)-DD. Moreover, the structures of the TRADD-DD:FADD-DD complexes were separately modeled from predicted structures in the protein data bank (PDB). The results of this study will have important applications in human diseases such as cancer, AIDS, degenerative and autoimmune diseases, and infectious diseases.

• Molecules and Cells
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• 제37권6호
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• pp.441-448
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• 2014

Inflammasomes are specialized signaling platforms critical for the regulation of innate immune and inflammatory responses. Various NLR family members (i.e., NLRP1, NLRP3, and IPAF) as well as the PYHIN family member AIM2 can form inflammasome complexes. These multiprotein complexes activate inflammatory caspases (i.e., caspase-1) which in turn catalyze the maturation of select pro-inflammatory cytokines, including interleukin (IL)-$1{\beta}$ and IL-18. Activation of the NLRP3 inflammasome typically requires two initiating signals. Toll-like receptor (TLR) and NOD-like receptor (NLR) agonists activate the transcription of pro-inflammatory cytokine genes through an NF-${\kappa}B$-dependent priming signal. Following exposure to extracellular ATP, stimulation of the P2X purinoreceptor-7 ($P2X_7R$), which results in $K^+$ efflux, is required as a second signal for NLRP3 inflammasome formation. Alternative models for NLRP3 activation involve lysosomal destabilization and phagocytic NADPH oxidase and /or mitochondria-dependent reactive oxygen species (ROS) production. In this review we examine regulatory mechanisms that activate the NLRP3 inflammasome pathway. Furthermore, we discuss the potential roles of NLRP3 in metabolic and cognitive diseases, including obesity, type 2 diabetes mellitus, Alzheimer's disease, and major depressive disorder. Novel therapeutics involving inflammasome activation may result in possible clinical applications in the near future.

• Journal of Acupuncture Research
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• 제30권1호
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• pp.57-70
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• 2013

This study was to investigated the effects of the bee venom on inhibition of cell growth via upregulation of death receptor expression in the A549 human lung cancer cells. Bee venom(1-5 ${\mu}g$/ml) inhibited the growth of A549 lung cancer cells by the induction of apoptotic cell death in a dose dependent manner. Consistent with apoptotic cell death, expression of TNFR1, Fas, death receptors(DR) 3, 4 and 6 was increased in the cells. Expression of DR downstream pro-apoptotic proteins including caspase-3, -9 and Bax was concomitantly increased, but the expression of Bcl-2, NF-${\kappa}B$ were inhibited by treatment with bee venom in A549 cells. Moreover, deletion of DR3, DR4 by small interfering RNA significantly reversed bee venom-induced cell growth inhibitory effect, whereas Apo3L strengthened anti-proliferative effect of bee venom through enhancement of DR3 expression. These results suggest that bee venom should exert anti-tumor effect through induction of apoptotic cell death in lung cancer cells via enhancement of death receptor expression, and that bee venom could be a promising agent for preventing and treating lung cancer.

• Journal of Periodontal and Implant Science
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• 제35권4호
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• pp.1081-1095
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• 2005

본 연구는 치주질환 주요 병인균주 중의 하나인 Porphyromonas gingivalis의 세균내독소가 마우스 대식 세포주인 RAW264.7 세포에서의 nitric oxide의 생성과 iNOS의 발현에 미치는 영향을 분석하고 그 기전을 규명하기 위해 수행되었다. Butanol추출법과 phenol-water법에 의해 P. gingivalis 381로부터 세균내독소를 추출하였으며, NO의 생성은 배양 상층액 내의 nitrite 농도를 측정하여 결정하였다. 또한, iNOS의 western blot 분석과 reverse transcription (RT)-PCR 산물의 분석을 수행하였다. P. gingivalis의 세균내독소는 부가적인 자극이 없는 상태에서도 iNOS의 발현과 NO 생성을 유발하였으며, NF- ${\kappa}B$, microtubule polymerization, protein tyrosine kinase, 그리고 protein kinase C 등이 P. gingivalis 세균내독소에 의한 NO 생성에 간여하는 것으로 여겨진다. 또한, P. gingivalis 세균내독소에 의한 NO 생성에는 L-arginine이 요구되었다. P. gingivalis 세균내독소에 의한 NO 생성은 염증성 치주질환의 발병과 진행에 있어 중요한 역할을 하는 것으로 여겨진다.

• BMB Reports
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• 제42권8호
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• pp.506-510
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• 2009

The Toll signalling pathway in invertebrates is responsible for defense against Gram-positive bacteria and fungi, leading to the expression of antimicrobial peptides via NF-$\kappa$B-like transcription factors. Gram-negative binding protein 3 (GNBP3) detects beta-1,3-glucan, a fungal cell wall component, and activates a three step serine protease cascade for activation of the Toll signalling pathway. Here, we showed that the recombinant N-terminal domain of Tenebrio molitor GNBP3 bound to beta-1,3-glucan, but did not activate down-stream serine protease cascade in vitro. Reversely, the N-terminal domain blocked GNBP3-mediated serine protease cascade activation in vitro and also inhibited beta-1,3-glucan-mediated antimicrobial peptide induction in Tenebrio molitor larvae. These results suggest that the N-terminal GNBP homology domain of GNBP3 functions as a beta-1,3-glucan binding domain and the C-terminal domain of GNBP3 may be required for the recruitment of immediate down-stream serine protease zymogen during Toll signalling pathway activation.

• BMB Reports
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• 제46권7호
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• pp.352-357
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• 2013

Atherosclerosis, which manifests as acute coronary syndrome, stroke, and peripheral arterial diseases, is a chronic inflammatory disease of the arterial wall. Prunella vulgaris, a perennial herb with a worldwide distribution, has been used as a traditional medicine in inflammatory disease. Here, we investigated the effects of P. vulgaris ethanol extract on TNF-${\alpha}$-induced inflammatory responses in human aortic smooth muscle cells (HASMCs). We found that P. vulgaris ethanol extract inhibited adhesion of monocyte/macrophage-like THP-1 cells to activated HASMCs. It also decreased expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin and ROS, No production in TNF-${\alpha}$-induced HASMCs and reduced NF-${\kappa}B$ activation. Furthermore, P. vulgaris extract suppressed TNF-${\alpha}$-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK). These results demonstrate that P. vulgaris possesses anti-inflammatory properties and can regulate TNF-${\alpha}$-induced expression of adhesion molecules by inhibiting the p38 MAPK/ERK signaling pathway.

• Journal of Ginseng Research
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• 제32권2호
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• pp.89-98
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• 2008

There are increasing evidences in the literatures on the potential role of ginsenosides in treating cardiovascular diseases. In this article, current information about ginsenosides-mediated vascular relaxation are reviewed. From the published studies using isolated organs, cell culture systems and animal models, ginsenosides are shown to relax blood vessels and improve blood flow through diverse mechanisms, including nitric oxide release by activating eNOS phosphorylation via PI3K/Akt and/or ERK1/2 pathways in endothelial cells, induction of inducible nitric oxide synthase through activation of NF-${\kappa}$B, reducing the intracelluar Ca$^{2+}$ levels by activating Ca$^{2+}$-activated K$^{+}$ channels in vascular smooth muscle cells and reducing platelet aggregation by decreasing thromboxane A$_2$ formation and intracelluar Ca$^{2+}$in platelets. In addition, the relevant clinical trials regarding the effects of ginsenosides on the cardiovascular disease are summarized, particulary focusing on managing hypertension and improving thrombotic disorders. Finally, antagonistic effects of ginsenosides on the prostaglandin H$_2$ receptor and scavenging effects on the generation of oxygen-derived free radicals in spontaneously hypertensive rats (SHR) are discussed.

• 약학회지
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• 제52권5호
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• pp.412-417
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• 2008

BAY11-7082 was initially found to be an anti-inflammatory drug with NF-${\kappa}B$ inhibitory property. In this study, we evaluated modulatory function of BAY11-7082 on U937 cell-cell adhesion induced by CD29 (${\beta}1$-integrins). BAY11-7082 strongly blocked functional activation of CD29 (${\beta}1$-integrins), as assessed by cell-cell adhesion assay. However, this compound did not block a simple activation of CD29, as assessed by cell-fibronectin adhesion assay. In particular, to understand molecular mechanism of BAY11-7082-mediated inhibition, the regulatory roles of CD29-induced actin cytoskeleton rearrangement under cell-cell adhesion and surface level of CD29 were examined using confocal and flow cytometic analysis. Interestingly, this compound strongly suppressed the molecular association of actin cytoskeleton with CD29 at cell-cell adhesion site. Moreover, BAY11-7082 also diminished surface levels of CD29 as well as its-associated adhesion molecule CD147, but not other adhesion molecules such as CD18 and CD43. Therefore, our data suggest that BAY11-7082 may be involved in regulating immune responses managed by CD29-mediated cell-cell adhesion.

• International Journal of Oral Biology
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• 제30권3호
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• pp.105-110
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• 2005

Periodontitis is a chronic infectious disease that leads to the destruction, one of the major cause of tooth loss in human. Osteoclast Differentiation Factor(ODF), also called as Receptor activator of NF-${\kappa}B$ ligand(RANKL), a surface-associated ligand on bone marrow stromal cells and osteoblasts, activates its cognate receptor RANK on osteoclast progenitor cells, which leads to differentiation of these mononucleated precursor cells. Osteoprotegerin(OPG), a decoy receptor, is released from stromal cells and osteoblasts to inhibit the interaction between RANKL and RANK. The experiment for the effect of pregnancy on gingival health showed greater gingival inflammation and edema during pregnancy, despite similar plaque index. There should be many factors affecting the periodontal health in pregnancy. In this experiment, we examined the direct effects of sex hormones(estrogen and progesterone) on the ODF/OPG expression in human gingival fibroblasts and periodontal ligament cells at the serum concentration of pregnancy. The ratio was high in the 1st trimester of pregnancy by estrogen and in the late 2nd trimester by progesterone. Therefore, the local periodontal destruction might be accelerated by these hormonal effect on the periodontal cells.