• The Korean Journal of Physiology and Pharmacology
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• v.19 no.1
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• pp.1-7
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• 2015

Our previous study has shown berberine prevents damage to the intestinal mucosal barrier during early phase of sepsis in rat through mechanisms independent of the NOD-like receptors signaling pathway. In this study, we explored the regulatory effects of berberine on Toll-like receptors during the intestinal mucosal damaging process in rats. Male Sprague-Dawlay (SD) rats were treated with berberine for 5 d before undergoing cecal ligation and puncture (CLP) to induce polymicrobial sepsis. The expression of Toll-like receptor 2 (TLR 2), TLR 4, TLR 9, the activity of nuclear factor-kappa B ($NF-{\kappa}B$), the levels of selected cytokines and chemokines, percentage of cell death in intestinal epithelial cells, and mucosal permeability were investigated at 0, 2, 6, 12 and 24 h after CLP. Results showed that the tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) level were significantly lower in berberine-treated rats compared to the control animals. Conversely, the expression level of tight junction proteins, percentage of cell death in intestinal epithelial cells and the mucosal permeability were significantly higher in berberine-treated rats. The mRNA expression of TLR 2, TLR 4, and TLR 9 were significantly affected by berberine treatment. Our results indicate that pretreatment with berberine attenuates tissue injury and protects the intestinal mucosal barrier in early phase of sepsis and this may possibly have been mediated through the TLRs pathway.

• Bulletin of the Korean Chemical Society
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• v.33 no.9
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• pp.3091-3094
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• 2012

• Korean System Dynamics Review
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• v.4 no.2
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• pp.131-151
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• 2003

Traffic congestion stems from the widespread desires of people to purse certain goals that inevitably overload existing roads every day. he a transportation policy, congestion toll system has been implemented in Seoul, since 1996. The growing concerns on whether the system would achieve sustained results in the future motivated us to investigate the effectiveness of this policy. Developing and running the congestion toll simulation model, we find that this policy is not an effective policy in the long m. The paper indicates the power of system dynamics approach as a tool for evaluating complex policy like a congestion toll, and suggest that city transportation policy maker should approach the problem with systems thinking and analyze the effectiveness of policy on the basis of understanding the dynamic relationships among subsystems.

• Journal of Veterinary Clinics
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• v.26 no.6
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• pp.520-523
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• 2009

The purporse of this study was to evaluate the quantitative differences in mRNA expression of TLR-2, -4, and -9 in normal equine eyes and eyes with equine recurrent uveitis (ERU). Normal equine eyes (n = 6) and eyes with naturally-occurring ERU (n = 6) were collected. Real time PCR assay was performed to compare mRNA expression of TLR-2, -4, and -9 between normal and ERU eyes. A significant up-regulation of TLR-2 and -9 mRNA in the ciliary body and TLR-2 mRNA in the iris was found in eyes with ERU compared to the mRNA levels in these same tissues of normal equine eyes. There were no remarkable differences observed in TLR-4 mRNA expression between normal eyes and eyes with ERU. The current data suggest the potential involvement of TLR-2 and -9 in the pathogenesis of ERU. However, further study is required to determine the role of TLRs in ERU.

• Biomedical Science Letters
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• v.18 no.3
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• pp.181-192
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• 2012

Toll-like receptors (TLRs) induce innate immune responses that are essential for host defense against invading microbial pathogens. In general, TLRs have two major downstream signaling pathways; myeloid differential factor 88 (MyD88) and Toll/IL-1R domain-containing adaptor inducing IFN-${\beta}$ (TRIF) leading to the activation of NF-${\kappa}B$ and IRF3. Numerous studies demonstrated that certain phytochemicals possessing anti-inflammatory effects inhibit NF-${\kappa}B$ activation induced by pro-inflammatory stimuli including lipopolysaccharide and tumor necrosis factor-${\alpha}$ ($TNF{\alpha}$). However, the direct molecular targets for such anti-inflammatory phytochemicals are not fully identified. In this paper, we will discuss about the molecular targets of phytochemicals in TLRs signaling pathways. These results present a novel anti-inflammatory mechanism of phytochemicals in TLRs signaling.

• Korean Journal of Food Science and Technology
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• v.39 no.5
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• pp.481-487
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• 2007

Toll-like receptors (TLRs) induce innate immune responses that are essential for host defenses against invading microbial pathogens, thus leading to the activation of adaptive immune responses. In general, TLRs have two major downstream signaling pathways: the MyD88- and TRIF-dependent pathways, which lead to the activation of $NF-{\kappa}B$ and IRF3. Numerous studies have demonstrated that certain phytochemicals possessing anti-inflammatory effects inhibit $NF-{\kappa}B$ activation induced by pro-inflammatory stimuli, including lipopolysaccharides and $TNF{\alpha}$. However, the direct molecular targets for such anti-inflammatory phytochemicals have not been fully identified. Identifying the direct targets of phytochemicals within the TLR pathways is important because the activation of TLRs by pro-inflammatory stimuli can induce inflammatory responses that are the key etiological conditions in the development of many chronic inflammatory diseases. In this paper we discuss the molecular targets of resveratrol, (-)-epigallocatechin-3-gallate (EGCG), and curcumin in the TLR signaling pathways. Resveratrol specifically inhibited the TRIF pathway in TLR3 and TLR4 signaling, by targetting TBK1 and RIP1 in the TRIF complex. Furthermore, EGCG suppressed the activation of IRF3 by targetting TBK1 in the TRIF-dependent signaling pathways. In contrast, the molecular target of curcumin within the TLR signaling pathways is the receptor itself, in addition to $IKK{\beta}$. Together, certain dietary phytochemicals can modulate TLR-derived signaling and inflammatory target gene expression, and in turn, alter susceptibility to microbial infection and chronic inflammatory diseases.

• Korean Journal of Food Science and Technology
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• v.41 no.5
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• pp.477-482
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• 2009

Toll-like receptors (TLRs) play a critical role in the induction of innate immune responses that are essential for host defense against invading microbial pathogens. In general, TLRs have two major downstream signaling pathways, namely MyD88- and TRIF-dependent pathways, leading to the activation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and interferon regulatory factor 3 (IRF3) and the expression of inflammatory mediators. TLR4 dimerization is required for the activation of downstream signaling pathways and may be one of the first lines of regulation in activating TLR-mediated signaling pathways. In this paper, the molecular targets of curcumin, 6-shogaol, and cinnamaldehyde in TLR signaling pathways will be discussed. Curcumin, 6-shogaol, and cinnamaldehyde with ${\alpha},{\beta}$-unsaturated carbonyl groups inhibit the dimerization of TLR4 induced by lipopolysaccharide, resulting in the downregulation of NF-${\kappa}B$ and IRF3. These results suggest that phytochemicals with the structural motif conferring Michael addition inhibit TLR4 dimerization, suggesting a novel mechanism for the anti-inflammatory activity of phytochemicals.

• Journal of Microbiology and Biotechnology
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• v.17 no.11
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• pp.1862-1867
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• 2007

An individual's immune response is critical for host protection from many different pathogens, and the responsiveness can be assessed by the amount of cytokine production upon stimulating bacterial components such as lipopolysaccharide (LPS). The difference between individuals in their peripheral blood mononuclear cells (PBMC) responsiveness to LPS, a Gram-negative endotoxin, was investigated from 27 healthy individuals. We observed a large variation in $IFN{\gamma}$ production among different individuals. The PBMC of the consistently three highest and three lowest $IFN{\gamma}$ producers were investigated. Since previous studies described that a single point mutation in the coding region of TLR2 and TLR4 is linked to the individual responsiveness to pathogenic bacterial infections, we first examined the known point mutations in the coding region of $TLR2^{Pro681His}$, $TLR4^{Pro714His}$ located in the cytoplasmic regions of the Toll-like domain as well as $TLR4^{Asp299Gly}$ located in the extracellular region. None of these mutations were associated with an individual's responsiveness to LPS, despite the presence of $TLR4^{Asp299Gly}$ mutation. Further investigation revealed that the variation of PBMC responsiveness to LPS among healthy individuals was due to constitutive expression levels of TLR4 and TLR2. This result is consistent with an aging-related low expression of Toll-like receptors in the mouse model of LPS responsiveness. The present study therefore suggests that the constitutive expression levels of TLR2 and TLR4 may contribute to the individual response to LPS.

• The Korean Journal of Malacology
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• v.31 no.3
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• pp.233-241
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• 2015

Toll-like receptors (TLRs) are a major pattern recognition receptor that recognize the structure of invading pathogen and play key roles by triggering immune response. In this study, we identified a sequence of TLR homolog and characterized at molecular level from the abalone (Haliotis discus hannai). Multiple alignments and phylogenetic analysis of abalone TLR protein belongs to the TLR 2/6. Expression level of abalone TLR 2/6 in the tissue was comparatively high in the mantle, gill, digestive duct, and hemocytes, but lowest in the muscle. Expression level of abalone TLR 2/6 mRNA in the mantle, gill, digestive duct, and hemocytes was 20-fold, 60-fold, 115-fold, 112-fold higher than in the muscle, respectively. Expression level of abalone TLR 2/6 mRNA in the mantle was steadily increased until 12 h and decreased post-infection with Vibrio parahemolyticus. While the expression level of abalone TLR 2/6 mRNA in the gill and hemocytes was drastically increased at 6 and 9 h post-infection with Vibrio parahemolyticus, respectively. These results suggest that abalone TLR 2/6 is conserved through evolution and may play roles similar to its mammalian counterparts.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.6
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• pp.636-642
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• 2007

Background: CpG DNA plays an important role in immune cell function. This study examined whether the temporal control of toll-like receptor (TLR)9 by CpG DNA can regulate the expression of matrix metalloproteinase-9(MMP-9). Methods and materials: Macrophages were cultured in the presence of 10% FBS. For the various MMP genes analysis, RT-PCR and real-time PCR were performed. In addition, zymography assay performed for the MMP activity. The phosphorylation assay did for the ERK1/2 and NF${\kappa}B$ activation, and luciferase promoter assay was for the NF${\kappa}B$ activity. Results: CpG DNA induced the mRNA expression of MMP-2, MMP-9, and MMP-13, but not of MMP-7, MMP-8, and MMP-12, in a time-dependent manner. Especially, the mRNA expression of MMP-9 was strongly induced by CpG DNA using real-time RT-PCR. The TLR9 inhibitor, chloroquine, suppressed CpG DNA-induced MMP-9 expression and its activity. Moreover, CpG DNA induced the phosphorylation of ERK and the inhibition of ERK by U0126 suppressed CpG DNA-induced MMP-9 expression and its activity. CpG DNA stimulated $I{\kappa}B-{\alpha}$ degradation and luciferase activity. In addition, pretreatment of SN-50, the inhibitor of NF${\kappa}B$, strongly blocked the CpG DNA-induced MMP-9 expression and activity. Conclusion: These observations suggest that CpG DNA may play important roles in the activation of macrophages by regulating the production of MMP-9 via the sequential TLR9-ERK-NF${\kappa}B$ signaling pathway.