• Biomolecules & Therapeutics
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• v.1 no.2
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• pp.236-243
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• 1993

Immunologic potential of DA-125, a new anthracycline antitumor antibiotic, was investigated using guinea pigs and mice. In antigenicity experiments, guinea pigs were sensitized subcutaneously with DA-125 or DA-125 incorporated in complete Freund's adjuvant (CFA) once a week for three weeks. No systemic anaphylaxis was induced by intravenous injection of DA-125 or DA-125 incubated with guinea pig serum after 3 weeks from the last sensitization. None of sera of these animals showed any passive cutaneous anaphylactic reaction (PCA) when DA-125 or DA-125 incubated with guinea pig serum was used as a challenging antigen in homologous PCA experiment. On the other hand the treatment of guinea pigs with ovalbumin Incorporated in CFA induced systemic anaphylactic reaction when challenged by intravenous injection of 5 mg/body of ovalbumin. Immunodiffusion test revealed no precipitating antibodies as detected in guinea pigs sensitized with DA-125. In 24-hour heterologous PCA reaction with sera of C57BL/6 mice immunized with DA-125 or DA-125 mixed with aluminum hydroxide gel (Alum), None of sera showed positive reaction when DA-125 or DA-125 incubated with rat serum was used as a challenging antigen. Sera of animals immunized with a mixture of ovalbumin and alum showed positive PCA reaction when 5 mg/body of ovalbumin was injected as a challenging antigen. In lymphocyte proliferation tests, spleen lymphocyte proliferation to PHA and LPS was similarly impaired by 12 mg/kg of DXR or 36 mg/kg of DA-125, and the immunodepressive activity of DA-125 showed a dose-dependent manner. From these results, it could be concluded that immunosupression of DA-125 would be comparable to that of DXR and that DA-125 would not induce systemic allergic reaction in its clinical use.

• The Journal of Pediatrics of Korean Medicine
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• v.7 no.1
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• pp.17-34
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• 1993

Experimental studies were done to know effect of insensible water loss of Hwangkitang(HKT) in mice. After administration of extract of HKT to the mice, changes of body temperature, body weight, serum Sodium and chloride ion was measured. And sametime, serum antibody to SRBC, delayed hypersensitivity and phagocytic activity of polymorphonuclear leukocytes(PMN) was measured to know immunologic effect. The results obtained as follows; 1. After exposure to $40^{\circ}C$ environment, increment of body temperature in treated group was slower than control group during first 40 minute, and no difference after 40 minute. 2. After exposured to $40^{\circ}C$ environment, decrement of body weight in treated group except administration group of 1.0g/kg extract of HKT was slower than control group during first 40 minute, and no difference after 40 minute. 3. After exposured to $40^{\circ}C$ environment, decrement of body weight in administration group of 4.0g/kg extract of HKT to mice was slower than control group during first 20 minute(p<0.005). 4. After exposure to $40^{\circ}C$ environment there was no stastical difference between treated group and control group in changes of serum sodium and chloride ion. 5. There was no statistical differences between treated group and control group in changes of serum antibody, delayed hypersensitivity and phagocytic activity of PMN.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.21 no.1
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• pp.34-42
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• 2018

Purpose: Monogenic inflammatory bowel disease (IBD) patients do not respond to conventional therapy and are associated with a higher morbidity. We summarized the clinical characteristics of monogenic IBD patients and compared their clinical outcomes to that of non-monogenic IBD patients. Methods: We performed a retrospective cohort study of all children <18 years old who were diagnosed with IBD between 2005 and 2016. A total of 230 children were enrolled. Monogenic IBD was defined as a presentation age less than 6 years old with confirmation of a genetic disorder. We subdivided the groups into monogenic IBD (n=18), non-monogenic very early-onset IBD (defined as patients with a presentation age <6 years old without a confirmed genetic disorder, n=12), non-monogenic IBD (defined as all patients under 18 years old excluding monogenic IBD, n=212), and severe IBD (defined as patients treated with an anti-tumor necrosis factor excluding monogenic IBD, n=92). We compared demographic data, initial pediatric Crohn disease activity index/pediatric ulcerative colitis activity index (PCDAI/PUCAI) score, frequency of hospitalizations, surgical experiences, and height and weight under 3rd percentile among the patients enrolled. Results: The initial PCDAI/PUCAI score (p<0.05), incidence of surgery per year (p<0.05), and hospitalization per year (p<0.05) were higher in the monogenic IBD group than in the other IBD groups. Additionally, the proportion of children whose weight and height were less than the 3rd percentile (p<0.05 and p<0.05, respectively) was also higher in the monogenic IBD group. Conclusion: Monogenic IBD showed more severe clinical manifestations than the other groups.

• Journal of Ginseng Research
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• v.33 no.3
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• pp.177-182
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• 2009

Macrophages play an important role in the first line of immunologic effects against tumor cells. The effects of nonsaponin red ginseng (NSRG) components on macrophage functions like tumoricidal activity, phagocytic activity, and NO production in young (8-weeks-old) and aged (82-weeks-old) male C57BL/6 mice were assessed in vitro, respectively. The treatment of tumor cells (melanoma B16 cells) with the supernatants of NSRG-treated macrophages resulted in an increase of cytotoxicity at 300 $\mu$g/ml in the aged mice, whereas the supernatants did not have a cytotoxic effect in the young mice. It was observed that the supernatants induced the increase of tumor cell proliferation at 150 $\mu$g/ml in the young mice, suggesting that the supernatants contain growth factors rather than cytotoxic molecules. In addition, NSRG alone had a direct cytotoxic effect on the B16 tumor cells. NSRG had no effect on the NO production by the macrophages in the young mice, while it significantly increased the level of NO release in the aged mice. There was no difference in the phagocytic activities of the macrophages by NSRG in both groups of mice. These results suggest that NSRG has differential effects on the macrophage functions in young and aged mice.

• Korean Journal of Veterinary Research
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• v.28 no.1
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• pp.105-110
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• 1988

To establish a laboratory animal model for study on development of diagnostic methods for infectious bovine rhinotracheitis virus(IBRV), experimental infection of the virus to rabbits immunosuppressed with dexamethasone(DX) were carried out. Results obtained throughout the experiments were as follows. When lymphocyte activity was measured by lymphocyte transformation to phytohaemagglutinin in parallel with total and differential leucocyte counting, both groups treated with 2.0mg DX once and 1.0mg DX daily showed marked immunosuppression between 5 to 72 hrs. after administration. The degree of suppression of lymphocyte activities was more remarkable in the latter group. IBRV PQ7 strain at $10^{7.5}\;TCID_{50}/0.2ml$ was inoculated into conjunctival sacs of rabbits immunosuppressed with DX and non-treated. During 3 weeks observation, the immunosuppressed groups revealed mild conjunctivitis, viremia and virus recovery by 33.3 to 100%, whereas the DX nontreated group showed viremia and virus recovery with no clinical conjunctivitis by one of three rabbits(33.3%). In conclusion, it was indicated that experimental infection of IBRV PQ7 strain to rabbit was limited in prerequisite to immunologic modification by administration of immunosuppressive drugs.

• Journal of Haehwa Medicine
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• v.15 no.1
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• pp.141-160
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• 2006

The obtained results are summarized as follows 1. New findings are reporting year by year as for the study related to Anti-inflammatory mechanism of Bee Venom therapy. 2. The Anti-inflammatory effect of Bee Venom therapy is achieved through counterirritation, stimulations to adrenal cortex, immuno-regulation, antioxidation, removal of free radicals, modulation of AGP gene induction. 3. The chief components of Bee Venom related to Anti-inflammatory effect are Melittin, MCD peptide, Apamin, Adolapin etc. 4. Melittin binds to secretory phospholipase A2 and inhibits its enzymatic activity. 5. Melittin blocks neutophil O2-production. 6. MCD peptide(Peptide 401) stimulates the mast cell secrets histamine, Anti-inflammatory effect caused by this is 'conterirritation'. 7. Melittin & Apamin have an anti-inflammatory effect by inducing cortisone secretion. 8. MCD peptide & Apamin increase immunologic fuction by stimulating hypophysis & adrenal cortex and have an anti-inflammatory effect by inhibiting synthesis of prostaglandin from arachidonic acid. 9. Adolapin have an anti-inflammatory effect by inhibiting COX. 10. Bee Venom have an anti-inflammatory effect by suppressing AGP($\alpha$-acid glycoprotein). 11. Bee Venom have an anti-inflammatory effect by inhibiting NO, iNOS, PLA2, COX-2, TNF-$\alpha$, IL-1, NF-${\kappa}B$, MAP kinase.

• Toxicological Research
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• v.34 no.1
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• pp.7-12
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• 2018

Laboratory animal models have been developed to investigate preventive or therapeutic effect of medicinal products, or occurrence or progression mechanism of atopic dermatitis (AD), a pruritic and persistent inflammatory skin disease. The murine model with immunologic phenomena resembling human AD was introduced, which demonstrated skewedness toward predominance of type-2 helper T cell reactivity and pathophysiological changes similar as human AD following 2,4-dinitrochlorobenzene (DNCB) sensitization and challenge. Molecular mechanism on the DNCB-mediated AD was further evaluated. Skin tissues were collected from mice treated with DNCB, and each tissue was equally divided into two sections; one for protein and the other for mRNA analysis. Expression of filaggrin, an important protein for keratinocyte integrity, was evaluated through SDS-PAGE. Level of mRNA expression for cytokines was determined through semi-quantitative reverse transcriptase polymerase chain reaction. Expression of filaggrin protein was significantly enhanced in the mice treated with DNCB compared with the vehicle (acetone : olive oil = 4 : 1 mixture) treatment group or the normal group without any treatment. Level of tumor necrosis factor-alpha and interleukin-18 mRNA expression, cytokines involved in activity of type-1 helper T ($T_H1$) cell, was significantly downregulated in the AD group compared with other control groups. These results suggest that suppression of $T_H1$ cell-mediated immune response could be reflected into the skin tissue of mice treated with DNCB for AD induction, and disturbance of keratinocyte integrity might evoke a compensatory mechanism.

• Journal of Veterinary Clinics
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• v.21 no.2
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• pp.93-96
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• 2004

We examined the responses of PBMCs to house dust mite (HDM) allergen in atopic and healthy, non-atopic dogs to identify differences in lymphocyte reactivity that might reflect the immunologic status of atopic dermatitis. Thirteen of 20 (65%) atopic dogs showed a positive lymphocyte proliferative response to HDM allergen. The rate of response was significantly higher in the atopic dogs than that in healthy, non-atopic dogs insensitive to the allergen (P = 0.007). The proliferative responses were positively correlated with the level of HDM-specific IgE in serum (P = 0.035), and were thereby confirmed to reflect the activity of lymphocytes competent to promote IgE production. These results suggest that HDM-specific lymphocytes were present in peripheral blood and played a role in the pathogenesis of canine atopic dermatitis.

• IMMUNE NETWORK
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• v.4 no.2
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• pp.88-93
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• 2004

Background: Bone marrow mesenchymal stem cells (MSC) inhibit the immune response of lymphocytes to specific antigens and dendritic cells (DC) are professional antigenpresenting cells whose function is to present antigen to naive T-lymphocytes with high efficiency and play a central role in the regulation of immune response. We studied the effects of MSC on DC to evaluate the relationship between MSC and DC in transplantation immunology. Methods: MSC were expanded from the bone marrow and DC were cultured from peripheral blood mononuclear cells (PBMNC) of 6 myelogenous leukemia after achieving complete response. Responder cells isolated from PBMNC and lysates of autologous leukemic cells are used as tumor antigen. The effect of MSC on the DC was analyzed by immunophenotype properties of DC and by proliferative capacity and the amount of cytokine production with activated PBMNC against the allogeneic lymphocytes. Also, cytotoxicity tests against leukemic cells studied to evaluate the immunologic effect of MSC on the DC. Results: MSC inhibit the CD83 and HLA-class II molecules of antigen-loaded DC. The proliferative capacity and the amount of INF-$\gamma$ production of lymphocytes to allogeneic lymphocytes were decreased in DC co-cultured with MSC. Also the cytotoxic activity of lymphocytes against leukemic cells was decreased in DC co-cultured with MSC. Conclusion: MSC inhibit the activation and immune response of DC induced by allogeneic or tumor antigen.

• Journal of Gastric Cancer
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• v.11 no.1
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• pp.16-22
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• 2011

Purpose: Eupatilin is an antioxidative flavone and a phytopharmaceutical derived from Artemisia asiatica. It has been reported to possess anti-tumor activity in some types of cancer including gastric cancer. Eupatilin may modulate the angiogenesis pathway which is part of anti-inflammatory effect demonstrated in gastric mucosal injury models. Here we investigated the anti-tumor effects of eupatilin on gastric cancer cells and elucidated the potential underlying mechanism whereby eupatilin suppresses angiogenesis and tumor growth. Materials and Methods: The impact of eupatilin on the expression of angiogenesis pathway proteins was assessed using western blots in MKN45 cells. Using a chromatin immunoprecipitation assay, we tested whether eupatilin affects the recruitment of signal transducer and activator of transcription 3 (STAT3), aryl hydrocarbon receptor nuclear translocator (ARNT) and hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) to the human VEGF promoter. To investigate the effect of eupatilin on vasculogenesis, tube formation assays were conducted using human umbilical vein endothelial cells (HUVECs). The effect of eupatilin on tumor suppression in mouse xenografts was assessed. Results: Eupatilin significantly reduced VEGF, ARNT and STAT3 expression prominently under hypoxic conditions. The recruitment of STAT3, ARNT and HIF-$1{\alpha}$ to the VEGF promoter was inhibited by eupatilin treatment. HUVECs produced much foreshortened and severely broken tubes with eupatilin treatment. In addition, eupatilin effectively reduced tumor growth in a mouse xenograft model. Conclusions: Our results indicate that eupatilin inhibits angiogenesis in gastric cancer cells by blocking STAT3 and VEGF expression, suggesting its therapeutic potential in the treatment of gastric cancer.