• The Korean Journal of Physiology and Pharmacology
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• v.18 no.1
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• pp.73-78
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• 2014

Cell death and survival are tightly controlled through the highly coordinated activation/inhibition of diverse signal transduction pathways to insure normal development and physiology. Imbalance between cell death and survival often leads to autoimmune diseases and cancer. Death receptors sense extracellular signals to induce caspase-mediated apoptosis. Acting upstream of CED-3 family proteases, such as caspase-3, Bcl-2 prevents apoptosis. Using short hairpin RNAs (shRNAs), we suppressed Bcl-2 expression in Jurkat T cells, and this increased TCR-triggered AICD and enhanced TNFR gene expression. Also, knockdown of Bcl-2 in Jurkat T cells suppressed the gene expression of FLIP, TNF receptor-associated factors 3 (TRAF3) and TRAF4. Furthermore, suppressed Bcl-2 expression increased caspase-3 and diminished nuclear factor kappa B (NF-${\kappa}B$) translocation.

• 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.

• Biomolecules & Therapeutics
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• v.18 no.3
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• pp.262-270
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• 2010

CD95 receptor is a member of tumor necrosis factor receptor family that mediates apoptosis in many cell types when bound by CD95 ligand or cross-linked by agonistic anti-CD95 antibodies. To determine the role of neutral sphingomyelinase (nSMase) on CD95-mediatd apoptosis, human Jurkat T lymphocytes were exposed to recombinant human CD95 ligand. Treatment with CD95 ligand induced cell death in a concentration and time-dependent manner. CD95-induced cell death was suppressed by inhibitors of SMase such as AY9944 or desipramine. Transfection with human nSMase1 siRNA plasmid into CD95 ligand-treated cells significantly prevented CD95-mediated cell death. CD95-mediated elevation of intracellular ceramide level detected by FACS analysis with anti-ceramide antibody was also decreased by nSMase1 siRNA. Knock-down of nSMase1 expression also blocked cytochrome c release into cytosol and caspase-3 cleavage in CD95-treated cells. Taken together, these results suggest that nSMase1 may play an important role in CD95-mediated apoptotic cell death in Jurkat T cells.

• Molecules and Cells
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• v.28 no.2
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• pp.125-130
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• 2009

Tacrolimus is a widely used T cell targeted immunosuppressive drug, known as a calcineurin inhibitor. However, the exact pharmacological effects of tacrolimus on $CD4^+$ T cells have yet to be elucidated. This study investigated the effects of tacrolimus on $CD4^+$ T cell subsets. Mouse or human $CD4^+$ T cells were cultured with immobilized anti-CD3/CD28 antibodies in the presence of tacrolimus. The cell division of $CD4^+$ T cells was analyzed using a flow cytometer according to the expression of Foxp3. The gene expression patterns of tacrolimus-exposed T cells were examined by quantitative PCR. In the case of conventional $CD4^+$ T cells (Tconv cells), tacrolimus inhibited T cell receptor stimulation-induced cell division. In contrast, the cell division of regulatory $CD4^+$ T cells (Treg cells) was even promoted in the presence of tacrolimus, especially in humans. Tacrolimus did not promote conversion of Tconv to Treg cells in mice. Furthermore, tacrolimus modified the expression levels of Foxp3-regulated T cell receptor signal related-genes, PTPN22 and Itk, in human Treg cells. Immunosuppressive effect of tacrolimus may be attributed to the relatively enhanced proliferation of Treg cells in association with altered gene expression levels of TCR signaling molecules.

• YAKHAK HOEJI
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• v.38 no.3
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• pp.238-249
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• 1994

The purpose of this research was to investigate effects of baicalin on the differentiation of preadipocytes, 3T3-L1, and to characterize the action of baicalin that affect the responses of 3T3-L1 cells during differentiation. In various culture conditions, effects of baicalin and adrenoreceptor agonists such as phenylephrine(PE) and isoproterenol(IPR) on cell differentiation were examined. Also, effects of the drugs on differentiation, triglyceride(TG) contents, expression of insulin receptor, cAMP contents, the cytosolic $Ca^{2+}$ levels, and amount of calmodulin(CaM) were examined. The results suggest that baicalin has adrenergic receptor blocking activity during the process of differentiation of 3T3-L1 cells and that in the early stage of the adipose conversion, the effect of baicalin on the adipocyte differentiation is mediated by the regulation of insulin receptor expression, but by alterations of the cAMP and the calcium metabolism in the late stage. These results also suggest that the action of baicalin may be significant in the lipid metabolism, lipogenic and lipolytic pathways, of adipose cells.

• 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.

• Biomolecules & Therapeutics
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• v.30 no.4
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• pp.299-308
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• 2022

T cells are attractive targets for the development of immunotherapy to treat cancer due to their biological features, capacity of cytotoxicity, and antigen-specific binding of receptors. Novel strategies that can modulate T cell functions or receptor reactivity provide effective therapies, including checkpoint inhibitor, bispecific antibody, and adoptive transfer of T cells transduced with tumor antigen-specific receptors. T cell-based therapies have presented successful pre-clinical/clinical outcomes despite their common immune-related adverse effects. Ongoing studies will allow us to advance current T cell therapies and develop innovative personalized T cell therapies. This review summarizes immunotherapeutic approaches with a focus on T cells. Anti-cancer T cell therapies are also discussed regarding their biological perspectives, efficacy, toxicity, challenges, and opportunities.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.7
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• pp.1085-1091
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• 2004

Bu-Zhong-Yi-Qi- Tang extracts is a traditional oriental medicine in a mixture type exhibiting strong anti-bacterial, analgesic, and chemopreventive activities. In this study, we have evaluated effects of the total and polysaccharide fraction of Bu-Zhong-Yi-Qi- Tang extracts on the T cell proliferation, cytokine production, and induction of IL-2 receptor and MHC class n. For this experiment, we established CD4$^{＋}$ CD8$^{[-10]}$ T cell line producing IL-2 and IFN-${\gamma}$ when stimulated with ovalbumin antigen in the presence of antigen presenting cells. The significant effect of Bu-Zhong-Yi-Qi-Tang on antigen-induced T cell proliferation in the presence of antigen presenting cells was observed. The proliferation and IFN-${\gamma}$ production of T cells was increased in a dose dependent manner, and expression of IL-2 receptor on T cells and MHC class n molecule on antigen presenting cells was also induced in the presence of Bu-Zhong-Yi-Qi-Tang polysaccharide fraction. It was demonstrated that polysaccharide fraction of Bu-Zhong-Yi-Qi-Tang stimulates the antigen-induced T cell proliferation and the production of IFN-${\gamma}$ possibly through the increase of IL-2 receptor and MHC class n expression. Therefore Bu-Zhong-Yi-Qi-Tang can be regarded as a natural and useful immunomodulator having a relatively nonotoxic property. Further studies are needed to better characterize the nature of Bu-Zhong- Yi-Qi-Tang extract.

• BMB Reports
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• v.47 no.5
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• pp.280-285
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• 2014

Cancer cells undergo uncontrolled proliferation, and aberrant mitochondrial alterations. Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial heat shock protein. TRAP1 mRNA is highly expressed in some cancer cell lines and tumor tissues. However, the effects of its overexpression on mitochondria are unclear. In this study, we assessed mitochondrial changes accompanying TRAP1 overexpression, in a mouse cell line, NIH/3T3. We found that overexpression of TRAP1 leads to a series of mitochondrial aberrations, including increase in basal ROS levels, and decrease in mitochondrial biogenesis, together with a decrease in peroxisome proliferator-activated receptor gamma coactivator-$1{\alpha}$ (PGC-$1{\alpha}$) mRNA levels. We also observed increased extracellular signal-regulated kinase (ERK) phosphorylation, and enhanced proliferation of TRAP1 overexpressing cells. This study suggests that overexpression of TRAP1 might be a critical link between mitochondrial disturbances and carcinogenesis.

• Toxicological Research
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• v.14 no.3
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• pp.371-377
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• 1998

We have cloned a soluble type human folate receptor(hFR type${\gamma}$) from human thymus cDNA library using the PCR amplification technique. To examine whether hFR type${\gamma}$ has a folate transport activity, CHO cells were transfected with the pcDNAhFR${\gamma}$ expression plasmid, and the stable cell line CHO/hFR${\gamma}$ expressing a high level of the hFR type${\gamma}$ was identified by northern and western blot analysis. The CHO/hFR${\gamma}$ cells produced a [$H^3$]folic acid binding protein in the culture medium. However, we couldn't detect any cell surface [$H^3$] folic acid binding and transport activities. The growth of the CHO/hFR${\gamma}$ cells was more rapidly inhibited than the wild type CHO cells in the low concentration folic acid media. These observations indicate that although soluble type human folate receptor can bind [$H^3$]folate, it does not involve in folate transport.