• The Journal of Korean Medicine
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• v.21 no.3
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• pp.40-50
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• 2000

Objectives : The progression of renal disease can be identified as a glomerulosclerosis by histological examination, and the basic mechanism of glomerulosclerosis is mesangial cell proliferation and mesangial matrix accumulation. ICAM-1, ${\beta}1-integrin$ and MHC-class II are known to attribute to the progression of glomerulosclerosis. They mediate cell-cell or cell-matrix interactions and are expressed in response to injury and inflammation. Up to now, there have been few satisfactory regimens to treat glomerular diseases except minimal change nephrotic syndrome, which can be improved by steroid therapy. Studies were performed in order to investigate whether Jinmu-tang has suppressive effects on some factors associated with the progression of glomerular disease, mesangial cell proliferation, fibronectin synthesis, ICAM-1, ${\beta}1-integrin$ and MHC-class II expression. Methods : Studies were performed with the method of surface enzyme immunoassays or flow cytometry after addition of peripheral blood mononuclear cells(PBMC) supernatants treated with Jinmu-tang, using the cultured human mesangial cells. Results : 1. The suppressive effect of Jinmu-tang on mesangial cell proliferation was higher than that of hydrocortisone. 2. Jinmu-tang has some suppressive effects on fibronectin synthesis, ICAM-1, expression, ${\beta}1-integrin$ expression and MHC-class II expression of mesangial cells, but was lower than hydrocortisone. Conclusions : Jinmu-tang generally shows some immunosuppressive effects. We carefully suggest that the above prescription may be applied to prevent the progression of renal disease or can be used as an adjuvant of or a substitute for steroid therapy.

• Childhood Kidney Diseases
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• v.24 no.1
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• pp.47-52
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• 2020

Pneumocystis pneumonia (PCP) is a rare disease in healthy people but a potentially fatal opportunistic infection by Pneumocystis jirovecii in immunocompromised patients with organ transplantation. We present three cases of PCP after kidney transplantation in pediatric patients. First case was a 4-year-old boy diagnosed with Denys-Drash syndrome and received living-donor kidney transplantation from his mother at age of 1. Second case was a 19-year-old male, with polycystic kidney disease, who received kidney transplantation from his mother at the age of 18. Third case was a 19-year-old female with chronic kidney disease of unknown etiology, who received kidney transplantation from her father at age of 15. These three patients who were on immunosuppressive therapy and completed of routine PCP prophylaxis for 6 months had presented with cough and dyspnea more than 1 year after transplantation. Chest x-ray all showed diffuse haziness of both lung fields, and bronchoalveolar lavage from bronchoscopy revealed Pneumocystisjirovecii infection. All patients showed clinical resolution with intravenous trimethoprim-sulfamethoxazole (TMP-SMX) therapy for at least 3 weeks and had continued secondary prophylaxis for another 6-12 months. This report suggests that clinicians should have suspicion for the possibilities of opportunistic infection such as PCP after kidney transplantation in children.

• Journal of Yeungnam Medical Science
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• v.15 no.2
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• pp.371-380
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• 1998

Systemic lupus erythematosus(SLE) is an autoimmune disease which may affect many different organs and disclose various clinical manifestations. Recently central nervous system(CNS) involvement has been recognized as an increasingly significant contributor to morbidity and mortality of SLE. The clinical manifestations of CNS-lupus are highly variable and range from mild cognitive dysfunction, movement disorder, headache, psychosis to life-threatening stroke and coma. Among the neuropsychiatric disorders encountered in patients with SLE, cerebrovascular disease has been a relatively rare complication. The diagnosis and management of CNS-lupus is difficult because of the lack of useful diagnostic methods. If cerebrovascular involvement is suspected, aggressive treatment such as high dose steroid, immunosuppressive therapy, plasma exchange may be required to reduce high mortality rate. We experienced 2 cases cerebrovascular dis eases occurring in SLE patients which presented with various neuropsychiatric manifestations. They were diagnosed as CNS-lupus by neuropsychiatric symptoms, brain MRI, and BEG, and showed good response to high dose steroid pulse therapy.

• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.536-544
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• 2021

5-amino salicylic acid (5-ASA) is a standard therapy for the treatment of mild to moderate forms of inflammatory bowel diseases (IBD) whereas more severe forms involve the use of steroids and immunosuppressive drugs. Hyaluronic acid (HA) is a naturally occurring non-sulfated glycosaminoglycan that has shown epithelium protective effects in experimental colitis recently. In this study, both 5-ASA (30 mg/kg) and HA (15 mg/kg or 30 mg/kg) were administered rectally and investigated for their potential complementary therapeutic effects in moderate or severe murine colitis models. Intrarectal treatment of moderate and severe colitis with 5-ASA alone or HA alone at a dose of 30 mg/kg led to a significant decrease in clinical activity and histology scores, myeloperoxidase activity (MPO), TNF-α, IL-6 and IL-1β in colitis mice compared to untreated animals. The combination of HA (30 mg/kg) and 5-ASA in severe colitis led to a significant improvement of colitis compared to 5-ASA alone. Combined rectal therapy with HA and 5-ASA could be a treatment alternative for severe cases of IBD as it was the only treatment tested that was not significantly different from the healthy control group. This study further underlines the benefit of searching for yet unexplored drug combinations that show therapeutic potential in IBD without the need of designing completely new drug entities.

• Journal of Radiation Protection and Research
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• v.48 no.1
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• pp.1-8
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• 2023

Background: The purpose of this study is to evaluate the immunosuppressive and antioxidant effects of a novel radioprotective agent using the vitamin E derivative 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol (TMG) and its effect on tumors, and to study its usefulness. Materials and Methods: In this study, C57BL/6NCrSlc mice were divided into four groups (control, TMG, radiation therapy [RT], and RT+TMG), using 10 mice in each group. In the TMG and 2 Gy+TMG groups, 500 mg/kg TMG was administered. Two groups (2 Gy and 2 Gy+TMG) among RT and RT+TMG groups were irradiated with 2 Gy in a single fraction, while the other two groups (6 Gy and 6 Gy+TMG) were irradiated locally with 6 Gy in three fractions. Results and Discussion: TMG positively affected CD4+ and CD8+ T lymphocytes. Tumor volumes and growth inhibition rates were compared. In order to evaluate how TMG administration affected tumor growth, Ehrlich cancer cells were injected into the thigh of mice, and the tumor volume and growth suppression rate were compared. Not only RT but also TMG alone inhibited tumor growth. If RT conducted to the mice with TMG, TMG could increase the number of leukocytes, primarily that of lymphocytes. TMG also inhibited tumor growth in addition to RT. Tumor growth was significantly inhibited in the 6 Gy+TMG group. Conclusion: In conclusion, TMG exerted an immunopotentiating effect mainly by increasing the white blood cell numbers including that of lymphocytes. In addition to RT, TMG also inhibited tumor growth. Therefore, TMG is considered to be a useful radioprotective agent in radiotherapy without tumor growth induction.

• IMMUNE NETWORK
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• v.16 no.1
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• pp.75-84
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• 2016

Cancer is one of the leading causes of morbidity and mortality worldwide; therefore there is a need to discover new therapeutic modules with improved efficacy and safety. Immune-(cell) therapy is a promising therapeutic strategy for the treatment of intractable cancers. The effectiveness of certain chemotherapeutics in inducing immunogenic tumor cell death thus promoting cancer eradication has been reported. Ginsenoside Rg3 is a ginseng saponin that has antitumor and immunomodulatory activity. In this study, we treated tumor cells with Rg3 to verify the significance of inducing immunogenic tumor cell death in antitumor therapy, especially in DC-based immunotherapy. Rg3 killed the both immunogenic (B16F10 melanoma cells) and non-immunogenic (LLC: Lewis Lung Carcinoma cells) tumor cells by inducing apoptosis. Surface expression of immunogenic death markers including calreticulin and heat shock proteins and the transcription of relevant genes were increased in the Rg3-dying tumor. Increased calreticulin expression was directly related to the uptake of dying tumor cells by dendritic cells (DCs): the proportion of CRT⁺CD11c⁺cells was increased in the Rg3-treated group. Interestingly, tumor cells dying by immunogenic cell death secreted IFN-γ, an effector molecule for antitumor activity in T cells. Along with the Rg3-induced suppression of pro-angiogenic (TNF-α) and immunosuppressive cytokine (TGF-β) secretion, IFN-γ production from the Rg3-treated tumor cells may also indicate Rg3 as an effective anticancer immunotherapeutic strategy. The data clearly suggests that Rg3-induced immunogenic tumor cell death due its cytotoxic effect and its ability to induce DC function. This indicates that Rg3 may be an effective immunotherapeutic strategy.

• IMMUNE NETWORK
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• v.8 no.1
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• pp.21-28
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• 2008

Background: A co-inhibitory molecule, B7-H4, is believed to negatively regulate T cell immunity by suppressing T cell proliferation and inhibiting cytokine production. However, the mechanism behind B7-H4-mediated tolerance remains unclear. Methods: Balb/c $(H-2^d)$ mice were fed with dendritic cell line, DC2.4 $(H-2^d)$ every day for 10 days. Meantime, mice were hydrodynamically injected with recombinant plasmid expressing B7-H4 fusion protein (B7-H4.hFc) or hFc via tail vein. One day after last feeding, mice were immunized with allogeneic B6 spleen cells. 14 days following immunization, mice were challenged with B6 spleen cells to ear back and the ear swelling was determined the next day. Subsequently, a mixed lymphocyte reaction (MLR) was also performed and cytokines profiles from the reaction were examined by sandwich ELISA. Frequency of immunosuppressive cell population was assayed with flow cytometry and mRNA for FoxP3 was determined by RT-PCR. Results: Tolerant mice given plasmid expressing B7-H4.hFc showed a significant reduction in ear swelling compared to control mice. In addition, T cells from mice given B7-H4.hFc plasmid revealed a significant hyporesponsiveness of T cells against allogeneic spleen cells and showed a significant decrease in Th1 and Th2 cytokines such as IFN-${\gamma}$, IL-5, and TNF-${\alpha}$. Interestingly, flow cytometric analysis showed that the frequency of CD4+CD25+FoxP3+ Tregs in spleen was increased in tolerant mice given recombinant B7-H4.hFc plasmid compared to control group. Conclusion: Our results demonstrate that B7-H4 synergistically potentiates oral tolerance induced by allogeneic cells by increasing the frequency of FoxP3+ CD4+CD25+ Treg and reducing Th1 and Th2 cytokine production.

• BMB Reports
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• v.52 no.5
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• pp.318-323
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• 2019

Mesenchymal stem cells (MSCs) are multipotent adult stem cells that present immunosuppressive effects in experimental and clinical trials targeting various rare diseases including inflammatory bowel disease (IBD). In addition, recent studies have reported tryptophanyl-tRNA synthetase (WRS) possesses uncanonical roles such as angiostatic and anti-inflammatory effects. However, little is known about the function of WRS in MSC-based therapy. In this study, we investigated if a novel factor, WRS, secreted from MSCs has a role in amelioration of IBD symptoms and determined a specific mechanism underlying MSC therapy. Experimental colitis was induced by administration of 3% DSS solution to 8-week-old mice and human umbilical cord blood-derived MSCs (hUCB-MSCs) were injected intraperitoneally. Secretion of WRS from hUCB-MSCs and direct effect of WRS on isolated $CD4^+$ T cells was determined via in vitro experiments and hUCB-MSCs showed significant therapeutic rescue against experimental colitis. Importantly, WRS level in serum of colitis induced mice decreased and recovered by administration of MSCs. Through in vitro examination, WRS expression of hUCB-MSCs increased when cells were treated with interferon-${\gamma}$ ($IFN-{\gamma}$). WRS was evaluated and revealed to have a role in inhibiting activated T cells by inducing apoptosis. In summary, $IFN-{\gamma}$-mediated secretion of WRS from MSCs has a role in suppressive effect on excessive inflammation and disease progression of IBD and brings new highlights in the immunomodulatory potency of hUCB-MSCs.

• Journal of Veterinary Clinics
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• v.31 no.3
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• pp.223-225
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• 2014

A 8-year-old, castrated male Maltese with difficulty in opening his mouth was presented. Masticatory muscle myositis (MMM) was diagnosed by 2M antibody test. After treatment of MMM with corticosteroids, range of jaw motion improved and was almost normal at 5 months. In dogs with MMM, early detection and aggressive immunosuppressive therapy are required to improve the prognosis.

• Tuberculosis and Respiratory Diseases
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• v.68 no.1
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• pp.29-33
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• 2010

Strongyloides stercoralis is an intestinal nematode that is a parasite to humans. The infecting filariform larvae of S. stercoralis enters the host body via the bloodstream, passes through the lungs, penetrates the alveoli, and then ascends the airway to transit down the esophagus into the small bowel. The infection can persist for decades without causing major symptoms and can elicit eosinophilia of varying magnitudes. Of note, this infection can also develop into a disseminated, often fatal, disease (hyperinfection) in patients receiving immunosuppressive corticosteroids. A 65-year-old man who was receiving corticosteroid therapy for the treatment of spinal stenosis was admitted to the emergency room with complaints of abdominal pain and severe dyspnea. We detected many S. stercoralis larvae in the sputum and in the bronchoalveolar-lavage sample collected by bronchoscopy. Here, we report a fatal case of strongyloidiasis with acute respiratory failure and intestinal perforation. In addition, we provide a brief review of the relevant medical literature.