• Molecular & Cellular Toxicology
• /
• v.1 no.3
• /
• pp.149-156
• /
• 2005

Di (n-ethylhexyl) phthalate (DEHP) is thought to mimic estrogens in their action, and are called endocrine disrupting chemicals. DEHP is used in numerous consumer products, especially those made of flexible polyvinyl chloride and have been reported to be weakly estrogenic. In this study, DEHP were tested for estrogenic properties in vitro models and with microarray analysis. First, the E-screen assay was used to measure the proliferation of DEHP in MCF-7 cells, a human breast cancer cell line. DEHP induced an increase in MCF-7 cell proliferation at concentration of $10^{-4}M$. Second, we carried out a microarray analysis of MCF-7 cells treated with DEHP using human c-DNA microarray including 401 endocrine system related genes. Of the genes analyzed, 60 genes were identified showing significant changes in gene expression resulting from DEHP. Especially, 4 genes were repressed and 4 genes were induced by DEHP compared to $17{\beta}-estradiol$. Among these genes, trefoil factor 3 (intestinal), breast cancer 1, early onset and CYP1B1 are involved in estrogen metabolism and regulation. Therefore it suggests that these genes may be associated with estrogenic effect of the DEHP on transcriptional level. The rationale is that, as gene expression is a sensitive endpoint, alterations of these genes may act as useful biomarkers to define more precisely the nature and level of exposure to kinds of phthalates.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.8
• /
• pp.3509-3515
• /
• 2015

Background: Diallyl disulfide (DADS) may exert potent anticancer action both in vitro and in vivo. Although its effects on cancer are significant, the underlying mechanisms remain unknown. In this study, we sought to elucidate possible links between DADS and pyruvate kinase (PKM2). Materials and Methods: $KG1{\alpha}$, a leukemia cell line highly expressing PKM2 was used with a cell counting kit (CCK)-8 and flow cytometry (FCM) to investigate the effects of DADS. Relationships between PKM2 and DADS associated with phosphorylation of EGFR, ERK1/2 and MEK, were assessed by western blot analysis. Results: In $KG1{\alpha}$ cells highly expressing PKM2, we found that DADS could affect proliferation, apoptosis and EGFR/ERK/PKM2 signaling pathways, abrogating EGF-induced nuclear accumulation of PKM2. Conclusions: These results suggested that DADS suppressed the proliferation of $KG1{\alpha}$ cells, providing evidence that its proapoptotic effects are mediated through the inhibition of EGFR/ERK/PKM2 signaling pathways.

• BMB Reports
• /
• v.46 no.8
• /
• pp.410-415
• /
• 2013

Adhesion molecules such as ICAM-1 are important in the infiltration of leukocytes into the site of inflammation. In this study, we investigated the inhibitory effects of curcumin on ICAM-1 expression and monocyte adhesiveness as well as its underlying action mechanism in the TNF-${\alpha}$-stimulated keratinocytes. Curcumin induced expression of heme oxygenase-1 (HO-1) in the human keratinocyte cell line HaCaT. In addition, curcumin induced Nrf2 activation in dose- and time-dependent manners in the HaCaT cells. Curcumin suppressed TNF-${\alpha}$-induced ICAM-1 expression and subsequent monocyte adhesion, which were reversed by the addition of tin protoporphyrin IX (SnPP), a specific inhibitor of HO-1, or HO-1 knockdown using siRNA. Furthermore, Nrf2 knockdown using siRNA reversed the inhibitory effect of curcumin on the TNF-${\alpha}$-induced ICAM-1 expression and adhesion of monocytes to keratinocytes. These results suggest that curcumin may exert its anti-inflammatory activity by suppressing the TNF-${\alpha}$-induced ICAM-1 expression and subsequent monocyte adhesion via expression of HO-1 in the keratinocytes.

• BMB Reports
• /
• v.49 no.1
• /
• pp.57-62
• /
• 2016

Up-regulation of adhesion molecules plays an important role in the infiltration of leukocytes into the skin during the development of various inflammatory skin diseases, such as atopic dermatitis. In this study, we investigated the modulatory effects of 2,3-dimethoxy-2′-hydroxychalcone (DMHC) on tumor necrosis factor (TNF)-α-induced intercellular adhesion molecule-1 (ICAM-1) expression and monocyte adhesiveness, as well as the molecular mechanisms underlying its action in the HaCaT human keratinocyte cell line. Pre-treating HaCaT cells with DMHC significantly suppressed TNF-α-induced ICAM-1 expression and subsequent monocyte adhesiveness. DMHC inhibited TNF-α-induced activation of NF-ᴋB. In addition, DMHC induced HO-1 expression as well as NRF2 activation. Furthermore, HO-1 knockdown using siRNA reversed the inhibitory effect of DMHC on TNF-α-induced ICAM-1 expression and adhesion of monocytes to keratinocytes. These results suggest that DMHC may inhibit TNF-α-induced ICAM-1 expression and adhesion of monocytes to keratinocytes by suppressing the signaling cascades leading to NF-ᴋB activation and inducing HO-1 expression in keratinocytes. [BMB Reports 2016; 49(1): 57-62]

• Korean Journal of Acupuncture
• /
• v.38 no.3
• /
• pp.133-139
• /
• 2021

Objectives : Parkinson's disease is a neurodegenerative disease caused by a decrease in the dopaminergic neurons in the substantia nigra. The abnormal expression of solute carrier family 6 member 4 (Slc6a4) has been reported in patients with Parkinson's disease. Methods : In this study, we used MPTP to examine the changes in the expression of Slc6a4 in the brain of mice with Parkinson's disease and investigate its effect on dopaminergic neuronal cell death. Results : In the examination of the Slc6a4 expression in the substantia nigra of MPTP-treated mice for 4 weeks. The gene expression was increased compared to the normal group. To investigate the relationship between Slc6a4 and dopaminergic neurons, we performed a study using siRNA of Slc6a4 in the dopaminergic neuronal cell line SH-SY5Y. Using the siRNA of Slc6a4 to evaluate gene expression, it revealed that the tyrosine hydroxylase (TH) expression increases when Slc6a4 decreases. Moreover, this confirms its effects on the dopaminergic neurons. Additionally, through the evaluation of factors related to apoptosis, in particular, it was established that the value of bax/bcl2 decreased and was affected. These results suggest that a decreased Slc6a4 expression induces an increase in TH expression, providing a mechanism of action for dopaminergic neurons regulated by Slc6a4 expression. Conclusions : Slc6a4 is deemed to be involved in the regulation of dopaminergic neurons, suggesting that an increased Slc6a4 expression induced by MPTP may influence a reduction of dopaminergic neurons.

• The Korea Journal of Herbology
• /
• v.27 no.6
• /
• pp.55-61
• /
• 2012

Objectives : Allium Hookeri (AH) is a traditional herb to treat inflammatory diseases in India and Myanmar. Recently, AH cultivation was succeeded in South Korea. This study was performed to evaluate the anti-inflammatory effects of Korean AH in RAW264.7 cells, mouse macrophage cell line. Methods : To evaluate the anti-inflammatory effects of root of AH, we prepared the 70% ethanol extract, then we examined the productions of nitrite, and pro-inflammatory cytokines. To examine the nitrite, and cytokines, the RAW264.7 cells were treated with AH, then stimulated with lipopolysaccharide (LPS, 500 ng/ml) for 24 h. Then the cells were harvested for griess assay, ELISA and real-time reverse transcription polymerase chain reaction (RT-PCR). Also to detect the ability of AH to induce heme oxygenase-1 (HO-1), we examined the HO-1 expression using real time RT-PCR and western blot. Furthermore, we examined the mitogen activated-protein kinases (MAPKs) and nuclear factor kappa B (NF-${\kappa}B$) activation to find out the underlying mechanisms. Results : AH ethanol extract significantly inhibited the productions of nitrite and interleukin (IL)-$1{\beta}$. AH treatment increased the HO-1 expression dramatically at 1 h, then peaked at 3 h. When the HO-1 was inhibited by tin (Sn) protoporphryin-IX (SnPP), the anti-inflammatory action of AH was reversed. AH treatment inhibited the activation of p38, but not extracelluar signal-regulated kinase (ERK 1/2) and c-Jun $NH_2$-terminal kinase (JNK) and also the degradation of inhibitory kappa B a (Ik-$B{\alpha}$) in the LPS-stimulated RAW 264.7 cells. Conclusions : These data could suggest that AH exerts anti-inflammatory influences through up-regulation of HO-1 and deactivation of p38.

• Journal of Korean Ophthalmic Optics Society
• /
• v.7 no.2
• /
• pp.189-195
• /
• 2002

The aim of this study was to investigate the action of benzalkonium chloride (BAC) used as a preservative in most ophthalmic topical solutions, on human corneal epithelial (HCE) cells in vitro. HCE cell line was exposed to BAC solutions at various concentrations (0.01%~0.0001%) for 15 minutes followed by 24 hours of cell recovery. Cell viability was assessed using MTT assay and chromatin condensation with a Hoechst 33342 test. The expression of membrane protein Fas and Fas ligand was examined by western blot and immunocytochemistry, and DNA fragmentation was studied by agarose gel electrophoresis. A significant decrease of membrane integrity with chromatin condensation was observed with BAC tested at concentrations of 0.005% and higher. BAC was cytotoxic preservatives in this study. An apoptotic mechanism appeared to be present at low concentrations of BAC, whereas a necrotic process appeared at higher concentrations. A functional Fas-mediated apoptotic pathway is present in cultured HCE cells and can be activated by upregulation of Fas expression with BAC.

• The Research Journal of the Costume Culture
• /
• v.5 no.3
• /
• pp.1-25
• /
• 1997

The consumers, who are characterized by gathering a wide scope of information and by putting into action immediately, have come to the new group searching for emotion and have played a leading role of market. The characgeristics of consumers are the fact that they have followed the street fashion with no-concept, independent of the trends which the brand has provide for consumers. Therefore it leads to a big gap between the fashion information for enterprises and market formation for consumer class. The principal purpose of this paper is to get closer the distance between the information which is used in merchandise plan and real market for consumers, and to suggest the new direction of information management system in order to enhance the hit rate of merchandise plan. The results are as follows : (1) It is shown the enterprises should divide the information data between fashion information and market information, and understand the mutual relationship of them, and regard the statistical data related on the change of sensitivity and desire in market specialized in attributes of street fashion as the emotional expression\`s view, and manage them by the feedback style. (2) It is shown that enterprises should fully understand the fashion factors in the line of fashion stream with the independence of theme in order to plan the merchandise effectively for market which are specialized in the duality that it has both conservation and innovation at the same time, and detect their change. (3) It is shown that in order to predict exactly, enterprises should reflect the statistical data and the emotional factors in planning the merchandise, bring up the systematic organization, expert system. (4) It is also shown that enterprises should make an effort to pursuit the discriminated brand through the feedback management in which the consumer\`s lasting desires are reflected.

• BMB Reports
• /
• v.48 no.3
• /
• pp.172-177
• /
• 2015

Upregulation of pro-inflammatory mediators contributes to ${\beta}$-cell destruction and enhanced infiltration of immune cells into pancreatic islets during development of type 1 diabetes mellitus. In this study, we examined the regulatory effects and the mechanisms of action of celastrol against cytotoxicity and pro-inflammatory immune responses in the RINm5F rat pancreatic ${\beta}$-cell line stimulated with a combination of interleukin-1 beta, tumor necrosis factor-alpha, and interferon-${\gamma}$. Celastrol significantly restored cytokine-induced cell death and significantly inhibited cytokine-induced nitric oxide production. In addition, the protective effect of celastrol was correlated with a reduction in pro-inflammatory mediators, such as inducible nitric oxide synthase, cyclooxygenase-2, and CC chemokine ligand 2. Furthermore, celastrol significantly suppressed cytokine-induced signaling cascades leading to nuclear factor kappa B (NF-${\kappa}B$) activation, including $I{\kappa}B$-kinase (IKK) activation, $I{\kappa}B$ degradation, p65 phosphorylation, and p65 DNA binding activity. These results suggest that celastrol may exert its cytoprotective activity by suppressing cytokine-induced expression of pro-inflammatory mediators by inhibiting activation of NF-${\kappa}B$ in RINm5F cells.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.34 no.1
• /
• pp.28-35
• /
• 2008

Purpose: The nitric oxide (NO) release by inducible nitric oxide synthase (iNOS) is the key events in macrophage response to lipopolysaccharide (LPS) which is suggested to be a crucial mediator for inflammatory and innate immune responses. NO is an important mediator involved in many host defense action and may also lead to a harmful host response to bacterial infection. However, given the importance of iNOS in a variety of pathophysiological conditions, control of its expression and signaling events in response to LPS has been the subject of considerable investigation. Materials and Methods: The Raw264.7 macrophage cell line was used to observe LPS-stimulated iNOS expression. The expression of iNOS is observed by Western blot analysis and real-time RT-PCR. Protein kinase C $(PKC)-{\alpha}$ overexpressing Raw264.7 cells are established to determine the involvement of $PKC-{\alpha}$ in LPS-mediated iNOS expression. $NF-{\kappa}B$ activity is measured by $I{\kappa}B{\alpha}$ degradation and $NF-{\kappa}B$ luciferase activity assay. Results: We found that various PKC isozymes regulate LPS-induced iNOS expression at the transcriptional and translational levels. The involvement of $PKC-{\alpha}$ in LPS-mediated iNOS induction was further confirmed by increased iNOS expression in $PKC-{\alpha}$ overexpressing cells. $NF-{\kappa}B$ dependent transactivation by LPS was observed and $PKC-{\alpha}$ specific inhibitory peptide abolished this activation, indicating that $NF-{\kappa}B$ activation is dependent on $PKC-{\alpha}$. Conclusion: Our data suggests that $PKC-{\alpha}$ is involved in LPS-mediated iNOS expression and that its downstream target is $NF-{\kappa}B$. Although $PKC-{\alpha}$ is a crucial mediator in the iNOS regulation, other PKC isozymes may contribute LPS-stimulated iNOS expression. This finding is needed to be elucidated in further study.