• IMMUNE NETWORK
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• v.4 no.4
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• pp.205-215
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• 2004

In the early host defense system, effector function of natural killer (NK) cells results in natural killing against target cells such as microbe-infected, malignant, and certain allogenic cells without prior stimulation. NK cell cytotoxicity is selectively regulated by homeostatic prevalence between a repertoire of both activating and inhibitory receptors, and the discrimination of untransformed cells is achieved by recognition of major histocompatibility complex (MHC) class I alleles through inhibitory signals. Although it is well known that the bipotential T/NK progenitors are derived from the common precusor, functional mechanisms in terms of the development of NK cells remain to be further investigated. NK cells are mainly involved in innate immunity, but recent studies have been reported that they also play a critical role in adaptive immune responses through interaction with dendritic cells (DC). This interaction will provide effector functions and development of NK cells, and elucidation of its precise mechanism may lead to therapeutic strategies for effective treatment of several immune diseases.

• Molecules and Cells
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• v.19 no.2
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• pp.180-184
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• 2005

IL-17 is a major proinflammatory cytokine secreted by activated T-lymphocytes that accumulates in the inflamed joints of rheumatoid arthritis (RA) patients. Additional IL-17-related molecules and their receptors have been discovered and may also contribute to RA pathogenesis. We examined the expression of the prototypic IL-17 (IL-17A) and its homologs, IL-17B-F, by RT-PCR analyses of synovial fluid mononuclear cells (SFMCs) and peripheral blood mononuclear cells (PBMCs) from RA patients. We also tested for induction of the IL-17 receptor homologs upon stimulation of the fibroblast-like synoviocytes (FLSs) of RA patients with IL-17. The patients' SFMCs expressed IL-17C, E and F in addition to IL-17A. As in the case of IL-17, IL-15 appears to be the major inducer of these homologs in RA SFMCs. We detected transcripts of IL-17R, as well as those of IL-17RB, C and D, in the FLSs of RA patients. Whereas IL-17R expression increased upon in vitro stimulation with IL-17, expression of IL-17RB, C and D was unchanged. However the possibility of cross-interaction between other IL-17 homologs and receptor isoforms remains to be investigated. Our data suggest that these additional homologs should also be considered as targets for immune modulation in the treatment of RA joint inflammation.

• Molecules and Cells
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• v.27 no.1
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• pp.5-14
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• 2009

The availability of effective vaccines has had the most profound positive effect on improving the quality of public health by preventing infectious diseases. Despite many successful vaccines, there are still old and new emerging pathogens against which there is no vaccine available. A better understanding of how vaccines work for providing protection will help to improve current vaccines as well as to develop effective vaccines against pathogens for which we do not have a proper means to control. Recent studies have focused on innate immunity as the first line of host defense and its role in inducing adaptive immunity; such studies have been an intense area of research, which will reveal the immunological mechanisms how vaccines work for protection. Toll-like receptors (TLRs), a family of receptors for pathogen-associated molecular patterns on cells of the innate immune system, play a critical role in detecting and responding to microbial infections. Importantly, the innate immune system modulates the quantity and quality of long-term T and B cell memory and protective immune responses to pathogens. Limited studies suggest that vaccines which mimic natural infection and/or the structure of pathogens seem to be effective in inducing long-term protective immunity. A better understanding of the similarities and differences of the molecular and cellular events in host responses to vaccination and pathogen infection would enable the rationale for design of novel preventive measures against many challenging pathogens.

• Archives of Pharmacal Research
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• v.20 no.6
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• pp.572-578
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• 1997

To gain further insight into how antiestrogens modulate cell function, the effects of antiestrogen on cell proliferation were studied in human breast cancer cells. We examined the effects of trans-tamoxifen on the proliferation of three human breast cancer cell lines that differed in their estrogen receptor contents. Trans-tamoxifen $(1{\mu}M)$ markedly inhibited the estrogen stimulated proliferation of MCF-7 human breast cancer cells that contained high levels of estrogen receptor $(1.15{\pm}0.03 pmole/mg protein)$ over that of control. In T47D cells that contained low levels of estrogen receptor $(0.23{\pm}0.05 pmole/mg protein)$, trans-tamoxifen $(1{\mu}M)$ showed minimal inhibition of estrogen stimulated cell proliferation over that of control. MDA-MB-231 cells, that contained no detectable levels of estrogen receptors, had their growth unaffected by trans-tamoxifen treatment. These results showed their sensitivity to growth inhibition by antiestrogen conrrelated well with their estrogen receptor content. Also we examined the effect of antiestrogen on cellular progestrone receptor level as well as plasminogen activator activity in MCF-7 cells. Trans-tamoxifen $(1{\mu}M)$ showed maximal inhibition of estrogen stimulated progestrone receptor level as well as plasminogen activator activity in MCF-7 cells that were stimulated by estrogen. It is not clear whether these inhibitions of progestrone receptor and plasminogen activator activity by estrogen are related to the antiestrogen inhibition of cell proliferation of MCF-7 cells. From the results of this study, it is clearly demonstrated that trans-tamoxifen is an antiestrogen in MCF-7 human breast cancer cells. Our data suggest that the biological effectiveness of trans-tamoxifen appear to result from its affinity of interaction with the estrogen receptor.

• Biomolecules & Therapeutics
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• v.18 no.4
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• pp.402-410
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• 2010

Although the overproduction of prostaglandin $E_2$ ($PGE_2$) in intestinal epithelial cells has been considered to be highly correlated with the colorectal carcinogenesis, the precise mechanism of action remains poorly elucidated. Accumulating evidence suggests that the PGE receptor (EP)-mediated signal transduction pathway might play an important role in this process. In the present study, we investigated the mechanism of action underlying $PGE_2$-mediated cell proliferation and the effect of resveratrol on the proliferation of human colon cancer cells in terms of the modulating $PGE_2$-mediated signaling pathway. $PGE_2$ stimulated the proliferation of several human colon cancer cells and activated growth-stimulatory signal transduction, including Akt and ERK. $PGE_2$ also increased the phosphorylation of GSK-$3{\beta}$, the translocation of ${\beta}$-catenin into the nucleus, and the expressions of c-myc and cyclin D1. Resveratrol, a cancer chemopreventive phytochemical, however, inhibited $PGE_2$-induced growth stimulation and also suppressed $PGE_2$-mediated signal transduction, as well as ${\beta}$-catenin/T cell factor-mediated transcription in human colon cancer cells. These findings present an additional mechanism through which resveratrol affects the regulation of human colon cancer cell growth.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2005.09a
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• pp.209-214
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• 2005

Immunoglobulins (IG) , T cell receptors (TR) and major histocompatibility complex (MHC) are major components of the immune system. Their experimentally determined three-dimensional (3D) structures are numerous and their retrieval and comparison is problematic. IMGT, the international ImMunoGeneTics information system$^{\circledR}$(http://imgt.cines.fr), has devised controlled vocabulary and annotation rules for the sequences and 3D structures of the IG TR and MHC. Annotated data from IMGT/3D sructure-DB, the IMGT 3D structure database, are used in this paper to compare 3D structure of the domains and receptor, and to characterize IG/antigen, peptide/MHC and TR/peptide/MHC interfaces. The analysis includes angle measures to assess receptor flexibility, structural superimposition and contact analysis. Up-to-date data and analysis results are available at the IMGT Web site, http://imgt.cines.fr.

• IMMUNE NETWORK
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• v.14 no.6
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• pp.265-276
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• 2014

The interactions between B7 molecules and CD28-family receptors are crucial in the regulation of adaptive cellular immunity. In cancer, the aberrant expression of co-inhibitory B7 molecules has been attributed to reduced anti-tumor immunity and cancer immune evasion, prompting the development of cancer therapeutics that can restore T cell function. Murine tumor models have provided significant support for the targeting of multiple immune checkpoints involving CTLA-4, PD-1, ICOS, B7-H3 and B7-H4 during tumor growth, and clinical studies investigating the therapeutic effects of CTLA-4 and PD-1 blockade have shown exceptionally promising results in patients with advanced melanoma and other cancers. The expression pattern of co-inhibitory B7 ligands in the tumor microenvironment has also been largely correlated with poor patient prognosis, and recent evidence suggests that the presence of several B7 molecules may predict the responsiveness of immunotherapies that rely on pre-existing tumor-associated immune responses. While monotherapies blocking T cell co-inhibition have beneficial effects in reducing tumor burden, combinatorial immunotherapy targeting multiple immune checkpoints involved in various stages of the anti-tumor response has led to the most substantial impact on tumor reduction. In this review, we will examine the contributions of B7- and CD28-family members in the context of cancer development, and discuss the implications of current human findings in cancer immunotherapy.

• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.655-660
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• 2023

Colorectal cancer (CRC) is one of the most high-risk cancers; however, it has been suggested that estrogen signaling in CRC could have a protective effect. Therefore, we focused on the function of the G protein-coupled estrogen receptor (GPER) among the estrogen receptors in CRC. In this study, we investigated the therapeutic effect of resveratrol via GPER in CRC (RKO and WiDr) cells, CRC cell-derived xenograft models, and organoids (30T and 33T). Resveratrol significantly suppressed cell viability and proliferation in highly GPER-expressing RKO cells compared to that in low GPER-expressing WiDr cells. In xenograft models, resveratrol also delayed tumor growth and exhibited a high survival rate depending on GPER expression in RKO-derived tumors. Furthermore, resveratrol significantly inhibited the viability of organoids with high GPER expression. Additionally, the anticancer effect of resveratrol on CRC showed that resveratrol rapidly responded to GPER, while increasing the expression of p-ERK and Bax and cleaving PARP proteins.

• IMMUNE NETWORK
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• v.11 no.5
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• pp.258-267
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• 2011

Background: Current management strategies attempt to diagnose rheumatoid arthritis (RA) at an early stage. Transcription profiling is applied in the search for biomarkers for detecting early-stage disease. Even though gene profiling has been reported using several animal models of RA, most studies were performed after the development of active arthritis, and conducted only on the peripheral blood and joint. Therefore, we investigated gene expression during the initial phase of collagen-induced arthritis (CIA) before the arthritic features developed in the thymus in addition to the peripheral blood and synovium. Methods: For gene expression analysis using cDNA microarray technology, samples of thymus, blood, and synovium were collected from CIA, rats immunized only with type II collagen (Cll), rats immunized only with adjuvant, and unimmunized rats on days 4 and 9 after the first immunization. Arrays were scanned with an Illumina bead array. Results: Of the 21,910 genes in the array, 1,243 genes were differentially expressed at least 2-fold change in various organs of CIA compared to controls. Among the 1,243 genes, 8 encode T-cell receptors (TCRs), including CD3${\zeta}$, CD3${\delta}$, CD3${\varepsilon}$, CD8${\alpha}$, and CD8${\beta}$ genes, which were down-regulated in CIA. The synovium was the organ in which the genes were differentially expressed between CIA and control group, and no difference were found in the thymus and blood. Further, we determined that the differential expression was affected by adjuvant more than Cll. The differential expression of genes as revealed by real-time RT-PCR, was in agreement with the microarray data. Conclusion: This study provides evidence that the genes encoding TCRs including CD3${\zeta}$, CD3${\delta}$, CD3${\varepsilon}$, CD8${\alpha}$, and CD8${\beta}$ genes were down-regulated during the initial phase of CIA in the synovium of CIA. In addition, adjuvant played a greater role in the down-regulation of the CD3 complex compared to CII. Therefore, the down-regulation of TCR gene expression occurred dominantly by adjuvant could be involved in the pathogenesis of the early stage at CIA.

• Clinical and Experimental Pediatrics
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• v.64 no.10
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• pp.504-510
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• 2021

Population screening of newborns is an extremely important and informative diagnostic approach that allows early identification of babies who are predisposed to the development of a number of serious diseases. Some of these diseases are known and have effective treatment methods. Neonatal screening enables the early diagnosis and subsequent timely initiation of therapy. This helps to prevent serious complications and reduce the percentage of disability and deaths among newborns and young children. Primary immunodeficiency diseases and primary immunodeficiency syndrome (PIDS) are a heterogeneous group of diseases and conditions based on impaired immune system function associated with developmental defects and characterized by various combinations of recurrent infections, development of autoimmune and lymphoproliferative syndromes (genetic defects in apoptosis, gene mutation Fas receptor or ligand), granulomatous process, and malignant neoplasms. Most of these diseases manifest in infancy and lead to serious illness, disability, and high mortality rates. Until recently, it was impossible to identify children with PIDS before the onset of the first clinical symptoms, which are usually accompanied by complications in the form of severe coinfections of a viral-bacterial-fungal etiology. Modern advances in medical laboratory technology have allowed the identification of children with severe PIDS, manifested by T- and/or B-cell lymphopenia and other disorders of the immune system. This review discusses the main existing strategies and directions used in PIDS screening programs for newborns, including approaches to screening based on excision of T-cell receptors and kappa-recombination excision circles, as well as the potential role and place of next-generation sequencing technology to increase the diagnostic accuracy of these diseases.