• IMMUNE NETWORK
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• v.19 no.1
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• pp.1.1-1.13
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• 2019

Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease characterized by production of autoantibodies to various nuclear antigens and overexpression of genes regulated by IFN-I called IFN signature. Genetic studies on SLE patients and mutational analyses of mouse models demonstrate crucial roles of nucleic acid (NA) sensors in development of SLE. Although NA sensors are involved in induction of antimicrobial immune responses by recognizing microbial NAs, recognition of self NAs by NA sensors induces production of autoantibodies to NAs in B cells and production of IFN-I in plasmacytoid dendritic cells. Among various NA sensors, the endosomal RNA sensor TLR7 plays an essential role in development of SLE at least in mouse models. CD72 is an inhibitory B cell co-receptor containing an immunoreceptor tyrosine-based inhibition motif (ITIM) in the cytoplasmic region and a C-type lectin like-domain (CTLD) in the extracellular region. CD72 is known to regulate development of SLE because CD72 polymorphisms associate with SLE in both human and mice and CD72^-/- mice develop relatively severe lupus-like disease. CD72 specifically recognizes the RNA-containing endogenous TLR7 ligand Sm/RNP by its extracellular CTLD, and inhibits B cell responses to Sm/RNP by ITIM-mediated signal inhibition. These findings indicate that CD72 inhibits development of SLE by suppressing TLR7-dependent B cell response to self NAs. CD72 is thus involved in discrimination of self-NAs from microbial NAs by specifically suppressing autoimmune responses to self-NAs.

• KSBB Journal
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• v.7 no.3
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• pp.201-208
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• 1992

Cell surface binding of epidermal growth factor(EGF) to EGF receptors was studied for a series of site-directed receptor mutants transfected into B82 mouse fibroblasts. Scatchard plots for truncation mutant receptors significantly lost nonlinearity for truncations below residue 1022. Transient plots of dissociation kinetics exhibited biphasic behavior for all receptor types, but the fraction of receptor in slow-dissociating form was reduced by an order of magnitude for the truncation mutants below residue 1022. Comparison of dissociation kinetics between control cells and cells treated with Triton X-100 revealed no significant variation for the slow-dissociating receptor form, but a noticeable variation was observed for the fast-dissociating receptor form when EGF receptors were truncated below residue 991. These results suggest that high affinity of EGF binding at cell surface depend on the EGF receptor cytoplasmic region.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.3
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• pp.179-187
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• 2011

Regulation of B cell receptor (BCR)-induced $Ca^{2+}$ signaling by CD40 co-stimulation was compared in long-term BCR-stimulated immature (WEHI-231) and mature (Bal-17) B cells. In response to long-term pre-stimulation of immature WEHI-231 cells to ${\alpha}$-IgM antibody (0.5~48 hr), the initial transient decrease in BCR-induced $[Ca^{2+}]_i$ was followed by spontaneous recovery to control level within 24 hr. The recovery of $Ca^{2+}$ signaling in WEHI-231 cells was not due to restoration of internalized receptor but instead to an increase in the levels of $PLC{\gamma}2$ and $IP_3R-3$. CD40 co-stimulation of WEHI-231 cells prevented BCR-induced cell cycle arrest and apoptosis, and it strongly inhibited the recovery of BCR-induced $Ca^{2+}$ signaling. CD40 co-stimulation also enhanced BCR internalization and reduced expression of $PLC{\gamma}2$ and $IP_3R-3$. Pre-treatment of WEHI-231 cells with the antioxidant N-acetyl-L-cysteine (NAC) strongly inhibited CD40-mediated prevention of the recovery of $Ca^{2+}$ signaling. In contrast to immature WEHI-231 cells, identical long-term ${\alpha}$-IgM pre-stimulation of mature Bal-17 cells abolished the increase in BCR-induced $[Ca^{2+}]_i$, regardless of CD40 co-stimulation. These results suggest that CD40-mediated signaling prevents antigen-induced cell cycle arrest and apoptosis of immature B cells through inhibition of sustained BCR-induced $Ca^{2+}$ signaling.

• Journal of Society of Preventive Korean Medicine
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• v.14 no.2
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• pp.77-89
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• 2010

Objectives : This study was performed to evaluate the effect of CJ(Cuscuta japonica Chois) on osteoclast differentiation and gene expression. Methods : The osteoclastogenesis and gene expression were determined in RANKL(receptor activator of nuclear factor kappa B ligand)－stimulated RAW 264.7. The results were summarized as followes. Results : CJ decreased the number of TRAP positive cell in RANKL-stimulated RAW264.7 cell. CJ decreased the expression of RANK(receptor activator of nuclear factor kappa B), $TNF{\alpha}$, and IL-6 in RANKL-stimulated RAW264.7 cell. CJ decreased the expression of iNOS and COX-2 in RANKL-stimulated RAW264.7 cell. CJ decreased the expression of Cathepsin K in RANKL-stimulated RAW264.7 cell. Conclusions : It is concluded that CJ might decrease the bone resorption resulted from decrease of osteoclast differentiation and it's related gene expression.

• BMB Reports
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• v.51 no.4
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• pp.188-193
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• 2018

Caffeoylserotonin (CaS), one derivative of serotonin (5-HT), is a secondary metabolite produced in pepper fruits with strong antioxidant activities. In this study, we investigated the effect of CaS on proliferation and migration of human keratinocyte HaCaT cells compared to that of 5-HT. CaS enhanced keratinocyte proliferation even under serum deficient condition. This effect of CaS was mediated by serotonin 2B receptor (5-HT2BR) related to the cell proliferation effect of 5-HT. We also confirmed that both CaS and 5-HT induced G1 progression via 5-HT2BR/ERK pathway in HaCaT cells. However, Akt pathway was additionally involved in upregulated expression levels of cyclin D1 and cyclin E induced by CaS by activating 5-HT2BR. Moreover, CaS and 5-HT induced cell migration in HaCaT cells via 5-HT2BR. However, 5-HT regulated cell migration only through ERK/AP-1/MMP9 pathway while additional Akt/NF-${\kappa}B$/MMP9 pathway was involved in the cell migration effect of CaS. These results suggest that CaS can enhance keratinocyte proliferation and migration. It might have potential as a reagent beneficial for wound closing and cell regeneration.

• IMMUNE NETWORK
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• v.22 no.5
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• pp.37.1-37.16
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• 2022

Autoimmune diseases are caused by a dysfunction of the acquired immune system. In a subset of autoimmune diseases, B cells escaping immune tolerance present autoantigen and produce cytokines and/or autoantibodies, resulting in systemic or organ-specific autoimmunity. Therefore, B cell depletion with monoclonal Abs targeting B cell lineage markers is standard care therapy for several B cell-mediated autoimmune disorders. In the last 5 years, genetically-engineered cellular immunotherapies targeting B cells have shown superior efficacy and long-term remission of B cell malignancies compared to historical clinical outcomes using B cell depletion with monoclonal Ab therapies. This has raised interest in understanding whether similar durable remission could be achieved with use of genetically-engineered cell therapies for autoimmunity. This review will focus on current human clinical trials using engineered cell therapies for B cell-associated autoimmune diseases.

• Molecular & Cellular Toxicology
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• v.5 no.2
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• pp.147-152
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• 2009

This study was conducted to evaluate the inflammatory mechanisms of LPS-stimulated BV-2 microglial cells. The inflammation mechanism was evaluated in BV-2 cells with or without LPS treated using the Affymetrix microarray analysis system. The microarray analysis revealed that B cell receptor signaling pathway, cytokine-cytokine receptor interaction, Jak-STAT signaling pathway, MAPK signaling pathway, Neuro-active ligand-receptor interaction, TLR signaling path-way, and T cell receptor signaling pathway-related genes were up-regulated in LPS stimulated BV-2 cells. Selected genes were validated using real time RTPCR. These results can help an effective therapeutic approach to alleviating the progression of neuro-in-flammatory diseases.

• International Journal of Oral Biology
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• v.39 no.1
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• pp.1-7
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• 2014

Neuromedin B (NMB) acts as a growth factor or a morphogen and plays a role in cancer progression. Indeed, the NMB receptor (NMB-R) is overexpressed in different types of tumors. In our current study, we investigated the involvement of NMB-R in the proliferation of oral cancer cells. Human oral squamous cell carcinoma (SCC) and human oral cancer cells, SCC-25 cells were found to be NMB-R-positive. The NMB-R antagonist PD168368 inhibited the proliferation of SCC-25 cells and reduced their colony formation capacity. We also found that PD168368 induced the cell cycle arrest and apoptosis of SCC-25 cells in a dose-/time-dependent manner. Overall, this antitumor activity of PD168368 in human oral cancer cells suggests that NMB-R is a potential target for the future prevention and treatment of human cancers.

• Biomedical Science Letters
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• v.23 no.3
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• pp.194-200
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• 2017

Bone-resorbing osteoclasts play a major role in maintaining bone homeostasis with bone-forming osteoblasts. Although it has been reported that A2B adenosine receptor (A2BAR) regulates osteoclast differentiation, its effects on apoptosis or proliferation of osteoclasts have been less-defined. Here, we demonstrate that A2BAR stimulation regulates macrophage-colony stimulating factor (M-CSF)-mediated osteoclast proliferation. Stimulation with a specific agonist of A2BAR, BAY 60-6583, significantly reduced M-CSF-mediated osteoclast proliferation in a time- and dose-dependent manner. In addition, A2BAR stimulation induced both apoptosis of the cells and cell arrest in the G1 phase with a decrease of cell number in the G2/M phase. Stimulation with BAY 60-6583 inhibited the activation of Akt by M-CSF, whereas M-CSF-induced ERK1/2 activation was not affected. These results suggest that the inhibition of M-CSF-mediated Akt activation by A2BAR stimulation increases apoptotic response of osteoclasts and induces cell cycle arrest in the G1 phase, thus contributing to the down-regulation of osteoclast proliferation.

• International Journal of Oral Biology
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• v.38 no.1
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• pp.37-42
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• 2013

Receptor activator of NF-${\kappa}B$ ligand (RANKL) is an essential cytokine for osteoclast differentiation, activation and survival. T lymphocytes such as $T_{17}$ cells, a subset of T helper cells that produce IL-17, play an important role in rheumatoid arthritic bone resorption by producing inflammatory cytokines and RANKL. It has not yet been clearly elucidated how T cell activation induces RANKL expression. T cell receptor activation induces the activation of nuclear factor of activated T cell (NFAT) and expression of its target genes. In this study, we examined the role of NFAT in T cell activation-induced RANKL expression. EL-4, a murine T lymphocytic cell line, was used. When T cell activation was induced by phorbol 12-myristate 13-acetate (PMA) and ionomycin, RANKL expression increased in a time-dependent manner. In the presence of cyclosporin, an inhibitor of NFAT activation, this PMA/ionomycin-induced RANKL expression was blocked. Overexpression of either NFATc1 or NFATc3 induced RANKL expression. Chromatin immunoprecipitation results demonstrated that PMA/ionomycin treatment induced the binding of NFATc1 and NFATc3 to the mouse RANKL gene promoter. These results suggest that NFATc1 and NFATc3 mediates T cell receptor activation-induced RANKL expression in T lymphocytes.