• Korean Journal of Microbiology
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• v.49 no.4
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• pp.301-308
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• 2013

Programmed Death-1 (PD-1) is one of the important immune-inhibitory molecules which was expressed in T cells, B cells, NKT cells, and macrophages activated by various immune activating factors. Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, is one of the crucial immunogens for PD-1 expression. However, there are only a few reports on the expression mechanisms of PD-1 in innate immune cells. In this study, we investigate the expression mechanisms of PD-1 in LPS-stimulated Raw264.7 cell lines by RT-PCR, Western Blot, flow cytometry as well as ChIP assay and co-immunoprecipitation. When Raw264.7 cells were stimulated with LPS, PD-1 expression was greatly up-regulated via PI3K and p38 signaling. Primary macrophages isolated from LPS-injected mice were also shown the increased expression of PD-1. In promoter assay, NF-${\kappa}B$ and IRF-1 binding regions in mouse PD-1 promoter are important for PD-1 expression. We also found that the co-activation of NF-${\kappa}B$ and IRF-1 is indispensable for the maximum PD-1 expression. These results indicate that the modulation of PD-1 expressed in innate immune cells could be a crucial for the disease therapy such as LPS-induced mouse sepsis model.

• Journal of Radiation Protection and Research
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• v.39 no.3
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• pp.134-141
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• 2014

Along with the wide use of radiotherapy in cancer treatment, there is growing interest in beneficial effect of low-dose irradiation (LDI) in cancer therapy. Therefore, we investigate how LDI affects immune responses in mice model. Total body irradiation (TBI) on C57BL/6 mice was given at low-dose rate of $1mGy{\cdot}min^{-1}$ using $^{137}Cs$ source at three times for consecutive three days. Hematological examination, total cell numbers of spleen, populations and characteristics of splenocytes were determined. Total numbers of RBC or platelet in irradiated mice showed no significant changes. WBC counts were decreased in a dose-dependent manner 2 days after TBI, however, these differences are gradually waned until 28 days. Dose-dependent decrease in the number of splenocytes of TBI mice at day 2 was also improved as time progressed. While the level of Foxp3 mRNA was decreased, the frequency of $CD4^+$ T cells and $CD69^+$ cells in spleen was increased at day 2 and 14. Fractionated low-dose TBI on mice exhibited normal body weight with no distinguishable behavior during whole experimental periods. These results suggest that some parameters of immune system could be altered and evaluated by fractionated low-dose TBI and be used to broaden boundary of low dose radiation research.

• Parasites, Hosts and Diseases
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• v.54 no.1
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• pp.93-96
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• 2016

Toxoplasmosis, a neglected tropical disease caused by the protozoan parasite Toxoplasma gondii, occurs throughout the world. Human T. gondii infection is asymptomatic in 80% of the population; however, the infection is life-threatening and causes substantial neurologic damage in immunocompromised patients such as HIV-infected persons. The major purpose of this study was to investigate the seroprevalence of T. gondii infection in subjects infected with HIV/AIDS in eastern China. Our findings showed 9.7% prevalence of anti-T. gondii IgG antibody in HIV/AIDS patients, which was higher than in intravenous drug users (2.2%) and healthy controls (4.7%), while no significant difference was observed in the seroprevalence of anti-Toxoplasma IgM antibody among all participants (P>0.05). Among all HIV/AIDS patients, 15 men (7.7%) and 10 women (15.9%) were positive for anti-T. gondii IgG antibody; however, no significant difference was detected in the seroprevalence of anti-Toxoplasma IgG antibody between males and females. The frequency of anti-Toxoplasma IgG antibody was 8.0%, 13.2%, 5.5%, and 0% in patients with normal immune function ($CD4^+$ T-lymphocyte count ${\geq}500cells/ml$), immunocompromised patients (cell count ${\geq}200$ and <500 cells/ml), severely immunocompromised patients (cell count ${\geq}50$ and <200 cells/ml), and advanced AIDS patients, respectively (cell count <50 cells/ml), while only 3 immunocompromised patients were positive for anti-T. gondii IgM antibody. The results indicate a high seroprevalence of T. gondii infection in HIV/AIDS patients in eastern China, and a preventive therapy for toxoplasmosis may be given to HIV/AIDS patients based on $CD4^+$ T lymphocyte count.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.161-166
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• 2014

Lung cancer is the most common causes of cancer-related deaths worldwide, and a lack of effective methods for early diagnosis has greatly impacted the prognosis and survival rates of the affected patients. Tumor-initiating cells (TICs) are considered to be largely responsible for tumor genesis, resistance to tumor therapy, metastasis, and recurrence. In addition to representing a good potential treatment target, TICs can provide clues for the early diagnosis of cancer. MicroRNA (miRNA) alterations are known to be involved in the initiation and progression of human cancer, and the detection of related miRNAs in TICs is an important strategy for lung cancer early diagnosis. As Hsa-miR-155 (miR-155) can be used as a diagnostic marker for non-small cell lung cancer (NSCLC), a smart molecular beacon of miR-155 was designed to image the expression of miR-155 in NSCLC cases. TICs expressing CD133 and CD338 were obtained from A549 cells by applying an immune magnetic bead isolation system, and miR-155 was detected using laser-scanning confocal microscopy. We found that intracellular miR-155 could be successfully detected using smart miR-155 molecular beacons. Expression was higher in TICs than in A549 cells, indicating that miR-155 may play an important role in regulating bio-behavior of TICs. As a non-invasive approach, molecular beacons could be implemented with molecular imaging to diagnose lung cancer at early stages.

• IMMUNE NETWORK
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• v.12 no.3
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• pp.113-117
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• 2012

FasL, perforin, $TNF{\alpha}$, IL-1 and NO have been considered as effector molecule(s) leading to ${\beta}$-cell death in autoimmune diabetes. However, the real culprit(s) of ${\beta}$-cell destruction have long been elusive despite intense investigation. Previously we have suggested $IFN{\gamma}/TNF{\alpha}$ synergism as the final effector molecules in autoimmune diabetes of NOD mice. A combination of $IFN{\gamma}$ and $TNF{\alpha}$ but neither cytokine alone, induced classical caspase-dependent apoptosis in murine insulinoma and pancreatic islet cells. $IFN{\gamma}$ treatment conferred susceptibility to $TNF{\alpha}$-induced apoptosis on otherwise resistant murine insulinoma cells by STAT1 activation followed by IRF-1 induction. Here we report that $IFN{\gamma}/TNF{\alpha}$ synergism induces apoptosis of human pancreatic islet cells. We also observed STAT1 activation followed by IRF-1 induction by $IFN{\gamma}$ treatment in human islet cells. Taken together, we suggest that $IFN{\gamma}/TNF{\alpha}$ synergism could be involved in human islet cell death in type 1 diabetes, similar to murine type 1 diabetes.

• Journal of Haehwa Medicine
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• v.19 no.2
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• pp.145-151
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• 2011

Backgrounds: Multidisciplinary approaches including surgery, chemotherapy, and radiation therapy are currently being performed to target various cancers in Western Medicine. However, some cancers still remain difficult to battle, which has long attracted many scientists for the discovery of new agents to fight cancers. Ginseng is one of the herbs used in Oriental Medicine including Korea, China and Japan. We have further investigated ginseng for its anticancer effect. Objective: This is a comprehensive review summary of anticancer effect of ginseng and ginsenoids as a possible agent for future cancer treatment. Methods: Data were retrieved from two web sites; www.pubmed.com and www.riss.kr, and authorized texts concerning anticancer effects of ginseng. From collected data, information on anticancer effect of ginseng was thoroughly sorted, restructured, then assessed. Results: Panax Ginseng C.A. Meyer belongs to Araliaceae Panax family, a perennial prairie plant with its root known as Ginseng Radix. Ginseng induces anticancer effect through cell cycle arrest, acceleration of apoptosis, anti-angiogenesis, and suppression of metastasis. Anticancer effect of ginseng may be due to single compound or multi-compound actions. Many studies report involvement of immune mechanisms of cytokines, Natural Killer (NK) cells, macrophages and some antibodies in enhancing anticancer effect of ginseng. In near future, possibility of applying these mechanisms into clinical trials is convinced. There were some important findings on saponin in ginsenoids in reviewing for this article; First, eradication of metastatic tumors were influenced by macrophage activation. Second, suppression of malignant melanoma cell metastasis to lung were induced by macrophage and NK cell activation in spleen with red ginseng acidic polysaccharide (RGAP). Third, final metabolites of M1, M4 had exerted anticancer effect of ginseng. Conclusion: Unknown anticancer mechanisms of ginseng have been studied for many years up until now. Ginseng is comprised of multiple bio-chemical compounds that create complex pharmaceutical interactions. Therefore, for its proper usage and safe prescription, studies on different types of ginseng and patients' susceptibility to ginseng according to their constitution and stages of the disease should be further pursued. More efforts are needed to understand the anticancer mechanisms of ginseng as well.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.18 no.1
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• pp.109-114
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• 1996

Plasmacytoma is one of the malignant neoplasm that originate in immunoglobulin-producing plasma cell, and occurrence in gingiva is known to be rare. About 7% of all patients with plasma cell malignancies present with solitary lesions in bone or soft tissues. In 30% to 40% of patients, the disease progresses to mulitiple myeloma on long-term follow-up. the incidence of progression to multiple myeloma is higher in patients with a bone lesion as compared with an extramedullary lesion. Several studies have shown a relatively favorable course for both these groups of patients, but many long-term studies have demonstrated the distinct difference in ultimate prognosis between patients with solitary lesions in bone and those with extramedullary lesions. The primary objective in the past has been to suppress the immune system to permit allotransplantation. But immunosuppressant also increases the incidence of malignant neoplasms in patients after allograft transplantation. We treated a 15-year patient with plasmacytoma on gingiva who had received kindny transplantation & immunosuppressant therapy. We excised this lesion & performed radiotherapy and had a favorable result.

• YAKHAK HOEJI
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• v.48 no.6
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• pp.335-344
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• 2004

Interleukin-2 (IL-2), a glycoprotein mainly secreted by CD4+ T helper Iymphocytes, has been developed to use recombinant cytokine to augment the immune response against cancer since IL-2 not only stimulates T Iymphocytes but also enhances natural killer (NK) cell activity. In order to evaluate the immunological safety of recombinant mouse IL-2 (rmIL-2) in cancer therapy, renal cell carcinoma was established in the flank by s.c. injection of renca cell line. Tumor-bearing BALB/c mice were treated with I.p. injections with $2{\times}10^5$ Lu rmIL-2. Even though the tumor size was diminished, there were not significant recovery of body and relative lymphoid organ weights including thymic atrophy in rmIL-2 immunotherapy. Distribution ratios of T cell subsets in thymus were analysed using flow cytometry. Without regard to dosage of rmIL-2, the ratio of CD3+CD4-CD8- T cells was increased in accordance with survival of solid tumor but that of CD4+CD8+ T cells was decreased dramatically. Emergence of autoantibodies (ANA, anti-dsDNA, and anti-histone) in blood was measured after rmIL-2 treatment. The results showed that the levels of ANA and anti-dsDNA did not significantly changed, but the level of anti-histone was increased significantly owing to rmIL-2 therapy. These results indicate rmIL-2 immunotherapy is to induce the autoimmune potential, and the anti-histone measurement as a biomarker of autoimmunity is useful in cancer immunotherapy.

• 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.

• IMMUNE NETWORK
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• v.23 no.6
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• pp.45.1-45.22
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• 2023

Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical's MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue disease-ILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone. Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited anti-apoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.