• IMMUNE NETWORK
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• v.12 no.2
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• pp.48-57
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• 2012

Acute viral encephalitis caused by neurotrophic viruses, such as mosquito-borne flaviviruses, is an emerging and re-emerging disease that represents an immense global health problem. Considerable progression has been made in understanding the pathogenesis of acute viral encephalitis, but the immune-pathological processes occurring during the progression of encephalitis and the roles played by various molecules and cellular components of the innate and adaptive systems still remain undefined. Recent findings reveal the significant contribution of Toll-like receptors (TLRs) and regulatory $CD4^+$ T cells in the outcomes of infectious diseases caused by neurotrophic viruses. In this review, we discuss the ample evidence focused on the roles of TLRs and $CD4^+$ helper T cell subsets on the progression of acute viral encephalitis. Finally, we draw attention to the importance of these molecules and cellular components in defining the pathogenesis of acute viral encephalitis, thereby providing new therapeutic avenues for this disease.

• BMB Reports
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• v.47 no.4
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• pp.184-191
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• 2014

Respiratory syncytial virus (RSV) is the leading cause of respiratory infection in infants and young children. Severe clinical manifestation of RSV infection is a bronchiolitis, which is common in infants under six months of age. Recently, RSV has been recognized as an important cause of respiratory infection in older populations with cardiovascular morbidity or immunocompromised patients. However, neither a vaccine nor an effective antiviral therapy is currently available. Moreover, the interaction between the host immune system and the RSV pathogen during an infection is not well understood. The innate immune system recognizes RSV through multiple mechanisms. The first innate immune RSV detectors are the pattern recognition receptors (PRRs), including toll-like receptors (TLRs), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), and nucleotide-biding oligomerization domain (NOD)-like receptors (NLRs). The following is a review of studies associated with various PRRs that are responsible for RSV virion recognition and subsequent induction of the antiviral immune response during RSV infection.

• 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.

• Proceedings of the PSK Conference
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• 2005.11a
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• pp.130-130
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• 2005

• Journal of Neurogastroenterology and Motility
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• v.24 no.4
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• pp.510-511
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• 2018

• Anatomy and Cell Biology
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• v.56 no.2
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• pp.228-235
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• 2023

Toll-like receptors (TLRs) are the mammalian ortholog of Drosophila melanogaster protein Toll, originally identified for its involvement in embryonic development. In mammals, TLRs are mainly known for their ability to recognize pathogen- or damage-associated molecular patterns and, consequently, to initiate the immune response. However, it is becoming clear that TLRs can play a role also in mammal embryo development. We have previously described TLR4 and TLR7 expression in developing mouse peripheral nervous system and gastrointestinal tract. In the present study, we extended the investigation of TLR4 and TLR7 to the respiratory system and to the two main accessory organs of the digestive system, the liver and pancreas. TLR4 and TLR7 immunostaining was performed on mouse conceptuses collected at different stages, from E12 to E18. TLR4 and TLR7 immunoreactivity was evident in the embryo pancreas and liver at E12, while, in the respiratory apparatus, appeared at E14 and E17, respectively. Although further studies are required to elucidate the specific role of these TLRs in embryo development, the differential spatiotemporal TLR4 and TLR7 appearance may suggest that TLR expression in developing embryos is highly regulated for a possible their direct involvement in the formation of the organs and in the acquisition of immune-related features in preparation for the birth.

• Biomedical Science Letters
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• v.19 no.2
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• pp.112-117
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• 2013

Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns (PAMPs) and regulate the activation of innate immunity. All TLR signaling pathways culminate in the activation of NF-${\kappa}B$, leading to the induction of inflammatory gene products such as cyclooxygenase-2 (COX-2). Triptolide (TP), a natural component of Tripterygium wilfordii Hook. F, has been used as folk remedies to treat many chronic diseases for many years. In the present report, we present biochemical evidence that TP inhibits the NF-${\kappa}B$ activation induced by polyriboinosinic polyribocytidylic acid (Poly[I:C], TLR3 agonist) and lipopolysaccharide (LPS, TLR4 agonist). TP also inhibits COX-2 expression induced by Poly[I:C] and LPS. These results suggest that TP can modulate the immune responses regulated by TLR3 and TLR4 signaling pathways.

• 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 Yeungnam Medical Science
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• v.30 no.1
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• pp.10-16
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• 2013

Background: Toll-like receptors (TLRs) are well-known pattern recognition receptors. Among the 13 TLRs, TLR2 is the most known receptor for immune response. It activates mitogen-activated protein kinases (MAPKs), which are counterbalanced by MAPK phosphatases [MKPs or dual-specificity phosphatases (DUSPs)]. However, the regulatory mechanism of DUSPs is still unclear. In this study, the effect of a TLR2 ligand (TLR2L, Pam3CSK4) on DUSP4 expression in Raw264.7 cells was demonstrated. Methods: A Raw264.7 mouse macrophage cell line was cultured in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum and 1% antibiotics (100 U/mL penicillin and 100 g/mL streptomycin) at $37^{\circ}C$ in 5% $CO_2$. TLR2L (Pam3CSK4)-mediated DUSP4 expressions were confirmed with RT-PCR and western blot analysis. In addition, the detection of reactive oxygen species (ROS) was measured with lucigenin assay. Results: Pam3CSK4 induced the expression of DUSP1, 2, 4, 5 and 16. The DUSP4 expression was also increased by TLR4 and 9 agonists (lipopolysaccharide and CpG ODN, respectively). Pam3CSK4 also induced ERK1/2 phosphorylation and ROS production, and the Pam3CSK4-induced DUSP4 expression was decreased by ERK1/2 (U0126) and ROS (DPI) inhibitors. U0126 suppressed the ROS production by Pam3CSK4. Conclusion: Pam3CSK4-mediated DUSP4 expression is regulated by ERK1/2 and ROS. This finding suggests the physiological importance of DUSP4 in TLR2-mediated immune response.