• The Korean Journal of Pesticide Science
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• v.11 no.3
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• pp.164-170
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• 2007

The concept of innate immunity in insects which refers to the first line of host defense constitutes the humoral and cellular components which are involved in recognition and actively participate in the elimination of the intruding foreign micro- or macro-organisms. Several recent studies suggest that juvenile hormone (JH) modulates the cellular immune reactions in response to pathogen. In this study, pyriproxyfen (a JH agonist as an insect growth regulator) was tested in its any inhibitory effect on the immune reactions of the beet armyworm, Spodoptera exigua. To this end, five different hemocyte morphotypes of final instar S. exigua were identified by phase contrast microscopy. Plasmatocytes and granular cells, which constitute about 90% of the total hemocyte count, were prominently distinguished based on their basophilic/acidophilic nature using Giemsa stain. The role of pyriproxyfen on the functional ability of hemocytes was analyzed using FITC-labeled Providencia vermicola for the phagocytic potential of the hemocytes. Both granular cells and plasmatocytes exhibited phagocytosis behavior. Pyriproxyfen significantly inhibited the phagocytosis of both cell types, proposing its novel action as an immunosuppressant.

• Journal of Yeungnam Medical Science
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• v.13 no.2
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• pp.159-172
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• 1996

대기오염물질이면서 동시에 생체내 화학반응의 산물이기도 한 nitric oxide(NO)는 그 생체내 분포가 광범위하고 생리적 역할이 다양하여, 최근의 생명과학 분야에서 가장 크게 주목받는 몇가지 연구대상 중 하나이다. 세포에서의 NO 산생은 nitric oxide synthase (NOS)에 의해 촉매되는데, 이들은 brain form (bNOS, neuronal; nNOS, NOS I), inducible form (iNOS), 및 endothelial form(eNOS)로 구분되는데, 이중 bNOS(nNOS)와 eNOS는 inducible form에 대비되는 constitutive form(cNOS)에 해당하므로 각각 ncNOS 와 ecNOS로도 불리운다. NOS는 아미노산인 L-arginine을 산소와 결합시켜 L-citrulline으로 변환시키면서 NO를 유리하고, 이 NO는 세포내의 guanylate cyclase를 활성화하여 cyclic GMP를 생산하거나, superoxide(O2-) 및 수소이온과 차례로 결합하여 반응성이 매우 높은 수산화기(-OH)를 발생시켜 세포독작용을 유발하기도 한다. 정상상태에서 뇌혈관내피세포의 ecNOS로 부터 유리된 NO는 혈관을 확장시켜 신경세포에 대한 산소공급을 원활히 유지해 주지만, 순환장애를 일으켰을 때는 뇌조직내의 iNOS로부터 대량의 NO가 유출되어 신경세포의 손상을 가져온다. 호흡기에서는 NO가 기도평활근을 이완시키고 폐혈류를 개선하므로, 미숙아나 성인의 호흡장애시에 소량의 NO를 흡입시키면 oxygenation을 호전시킬 수 있다. 그러나 대기오염이나 흡연 등으로 대량의 NO를 흡입할 경우 치명적인 폐부종이나 methemoglobin혈종을 일으킬 수 있다. 순환계에서는 cNOS가 혈관을 확장시켜 조직의 혈류를 유지하는데 일익을 담당한다. 세균내 독소(lipopolysaccharide; LPS)나 각종 명역조절물질들이 혈관내피세포와 혈관평활근세포로 부터 과다한 NO를 유리시키면 혈압이 급격히 떨어져 순환허탈상태에 빠지게 된다. 심장에서는 관상혈관 내피세포의 eNOS가 심근의 혈류를 유지해 주지만 허혈이나 세균내독소 또는 면역조절물질 등에 의하여 심근세포나 침윤된 대식세포의 iNOS로 부터 과량의 NO가 유리되면 심근세포의 손상이 초래된다. 신장에서는 내피세포의 cNOS에 의하여 사구체여과가 조절되고 있는데, 세균내독소나 면역 조절물질 등에 의하여 사구체관막세포(mesangial cell)등의 iNOS로 부터 과량의 NO가 유리되면 신조직과 사구체의 손상을 초래한다. 위와 같이 대부분의 장기에서 ecNOS는 조직의 혈류를 유지하는 역할을 하며, iNOS는 애초 세균 등 침입자에 대한 세포독작용이 그 존재 목적이라고 풀이할 수 있겠으나 일종의 부작용으로 자체조직의 손상을 초래하게 되는 것으로 본다. 따라서 NO와 관련된 각종 병변의 치료를 위해서는 NOS의 비선택성 억제제인 arginine 유도체 보다는 iNOS에 대한 선택적 억제제인 S-methylisothiourea(SMT), aminoethylisothiourea(AETU), aminoguanidine (AMG), agmatine, L-canavanine, transforming growth factor b1(TGF-b1) 등의 사용을 검토해 보는 것이 타당할 것으로 사료된다.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.1
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• pp.38-48
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• 2022

Carcinoembryonic antigen (CEA) is an oncofetal antigen primarily detected in the peripheral blood of cancer patients, particularly in those with colorectal cancer. CEA is considered a valuable target for antigen-specific immunotherapy. In this study, we induced the anti-tumor immunity for CEA through the administration of a dendritic cell (DC) vaccine. However, there was a limitation in inducing tumor regression in the DC vaccinated mice. To enhance the efficacy of anti-tumor immunity in MC38/CEA2 tumor-bearing mice, we evaluated the effects of DC vaccine in combination with cyclophosphamide (CYP). Administration of CYP 100 mg/kg in mice resulted in significant inhibition of tumor growth in the 2-day tumor model, whereas a lower inhibition of tumor growth was seen in the 10-day tumor model. Therefore, the 10-day tumor model was selected for testing chemo-immunotherapy. The combined CYP and DC vaccine not only increased tumor antigen-specific immune responses but also induced synergistic anti-tumor immunity. Furthermore, the adverse effects of CYP such as weight loss and immunosuppression by regulatory T cells and myeloid-derived suppressor cells showed a significant reduction in the combined chemo-immunotherapy treatment compared with CYP alone. Our data suggest that chemoimmunotherapy with the DC vaccine may offer a new therapeutic strategy to induce a potent anti-tumor effect and reduce the adverse effects of chemotherapy.

• Journal of Life Science
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• v.29 no.7
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• pp.824-835
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• 2019

In recent decades, oncolytic viruses (OVs) have extensively been investigated as a potential cancer drug. Oncolytic viruses have primarily the unique advantage in the fact that they can only infect and destroy cancer cells. Secondary, oncolytic viruses induce the activation of specific adaptive immunity which targets tumor-associated antigens that were hidden during the initial cancer progression. In 2015, one genetically modified oncolytic virus, talimogene laherparepvec (T-VEC), was approved by the American Food and Drug Administration (FDA) for the treatment of melanoma. Currently, various oncolytic viruses are being investigated in clinical trials as monotherapy or in combination with preexistent cancer therapies like immunotherapy, radiotherapy or chemotherapy. The efficacy of oncolytic virotherapy relies on the balance between the induced anti-tumor immunity and the anti-viral response. Despite the revolutionary outcome, the development of oncolytic viruses for the treatment of cancer faces a number of obstacles such as delivery method, neutralizing antibodies and induction of antiviral immunity due to the complexity, variability and reactivity of tumors. Intratumoral administration has been successful reducing considerably solid tumors with no notable side effects unfortunately some tumors are not accessible (brain) and require a systemic administration of the oncolytic viruses. In order to overcome these hurdles, various strategies to enhance the efficacy of oncolytic viruses have been developed which include the insertion of transgenes or combination with immune-modulatory substances.

• The Journal of the Korean Society for Microbiology
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• v.16 no.1
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• pp.49-55
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• 1981

Recent studies have demonstrated that histamine could have a modulatory influence on the immune response in vitro and in vivo. However, the effect of histamine on immune response in mice has not been extensivley analyzed. In the present study the regulatory effects of cimetidine, a histamine-2-receptor antagonist(H2 blocker) and histamine on the immune response to sheep red blood cells(SRBC) were evaluated in mice. Mice pretreated with daily intraperitoneal injection of varying concentrations of cimetidine for 14 days were immunized intraperitoneally with various concentrations of SRBC($10^6,\;10^7,\;and\;10^8$ cells) and challenged 4 days post immunization. The cellular immune response was determined by measuring the footpad swelling reaction. Footpad swelling reaction of each mouse was measured at 3hr(Arthus) reaction) and 24 or 48 hr(delayed reactions) after challenge. The humoral immune response was determined by measuring hemagglutinins to SRBC. Histamine in varying concentrations($10^{-1},\;10^{-3}\;and\;10^{-5}M$(was added in SRBC suspension at the time of antigen challenge into footpad, and 24-hr delayed type hypersensitivity(DTH) was measured. Cimetidine in varying concentrations(10, 50, 250, 1250 and 6250${\mu}g$) enhanced 24-hr DTH and this enhancement of DTH was more pronounced at 250${\mu}g$ of cimetidine. However, there were no significant differences between the cimetidine-pretreated groups and controls in Arthus reaction and hemagglutinin titers. Histamine suppressed the DTH in the dose-dependent fashion. This suppression was more pronounced at lower concentration of immunizing antigen($10^7\;and\;10^6$ SRBC). However, histamine did not diminish the DTH at higher concentration of antigen($10^8$ SRBC). These results present the evidences which strongly suggest that cimetidine enhances the cell-mediated immune response but not significantlly influences the humoral immune response and that exogenous and endogenous histamine is involved in the modulation of cellular immune response as well as immediate hypersensitivity.

• Korean Journal of Transplantation
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• v.31 no.4
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• pp.157-169
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• 2017

Regulatory T cells (Treg) naturally rein in immune attacks, and they can inhibit rejection of transplanted organs and even reverse the progression of autoimmune diseases in mice. The initial safety trials of Treg against graft-versus-host disease (GVHD) provided evidence that the adoptive transfer of Treg is safe and capable of limiting disease progression. Supported by such evidence, numerous clinical trials have been actively investigating the efficacy of Treg targeting autoimmune diseases, type I diabetes, and organ transplant rejection, including kidney and liver. The limited quantity of Treg cells harvested from peripheral blood and subsequent in vitro culture have posed a great challenge to large-scale clinical application of Treg; nevertheless, the concept of CAR (chimeric antigen receptor)-Treg has emerged as a potential resolution to the problem. Recently, two CAR-T therapies, tisagenlecleucel and axicabtagene ciloleucel, were approved by the US FDA for the treatment of refractory or recurrent acute lymhoblastic leukemia. This approval could serve as a guideline for the production protocols for other genetically engineered T cells for clinical use as well. The phase I and II clinical trials of these agents has demonstrated that genetically engineered and antigen-targeting T cells are safe and efficacious in humans. In conclusion, both the promising results of Treg cell therapy from the clinical studies and the recent FDA approval of CAR-T therapies are paving the way for CAR-Treg therapy in clinical use.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.3 s.47
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• pp.345-352
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• 2004

There are two paradigms to explain the atopic dermatitis. The first is outside-inside paradigm and the second is inside-outside paradigm. According to the outside-inside paradigm the best way to treat the atopic dermatitis is recovery of skin barrier function. The barrier function is maintained by the specific structure of stratum corneum, which is constructed from corneocytes and intercellular lipids. In terms of lipid structures of SC in atopic dermatitis and lamellar ichthyosis, they contain more fluid hexagonal gel structures in SC and show deficiencies in free fatty acids, especially long chains and certain ceramides. With this reason, moisturizer which has the lamellar structure and restoring function of intrinsic intercellualr long periodicity phase can maintain and restore the lamellar structure of intercellular lipids in SC. The moisturizers containing ceramide or pseudoceramide also seem to be reasonable therapy for atopic dermatitis and several skin diseases, which interrelated with impaired skin harrier. By the way, according to the inside-outside paradigm, immune response including helper T cells, IgE, eosinophils is related. It is effective treatment of atopic dermititis to restore imbalance between Th1 and Th2 cells. Even though several kinds of immune-suppressor were introduced, these can affect the intrinsic immune function. SPC and S1P, metabolites of ceramide, would be interesting because they have the function of wound healing and immune modulating properties.

• Korean Journal of Pharmacognosy
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• v.28 no.4
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• pp.286-292
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• 1997

We studied the screening condition for immune regulatory responsor. We focused on the T-lymphocytes leer this purpose. Mouse fetal thymic organ culture (FTOC) system and flow cytometric analysis were mainly used in this experiment. Even if FTOC is carried out in vivo condition, the pattern of thymic development in the condition of FTOC is similar to that of in vivo condition. In this regard, FTOC system might be very powerful tool to screen the immune regulator, especially concerning on T cells. To establish the optimum condition of FTOC to screen the Immune regulator, we focused on the optimum amount of dose and culture period. The cell number and surface antigens on T cells were also analysed by using hemacytometer and flow cytometer. To monitor the differentiation event, anti-CD3, anti-CD4 and anti-CD8 antibodies were used. Alkoxyglycerol and Phellodendri Cortex were used fur positive and negative control, respectively. Astragalus membranceus was used as test sample. From our analysis, we reached to conclusions that the best dose of extract is $50\;{\mu}g/ml$ of culture medium, the best culture period is for 9 days, and ethanol used as solvent has no toxicity to FTOC.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.1
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• pp.14-19
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• 2011

In this study, we extracted a whole polysaccharide fraction from the sea hare, Aplysia kurodai, and screened its functional properties using cell lines. The functionalities of polysaccharide and glycosaminoglycan (GAG) were investigated with RAW 264.7 cell lines. The crude polysaccharides and GAG purified DEAE-Sepharose chromatography did not show the toxicity on RAW 264.7 cell line in the range of $10\sim200{\mu}g$/mL, whereas they increased the cell growth rate. The crude polysaccharides and purified GAG also increased the production of NO, interleukin-6 and tumor necrosis factor-$\alpha$ on RAW 264.7 cell. Particularly, the purified GAG inhibited the proliferation of stomach cancer cell line, AGS, up to 40% for 72 hr incubation, but not the intestinal epithelial IEC-6 cell lines.

• Journal of Life Science
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• v.21 no.4
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• pp.515-520
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• 2011

This study was carried out to evaluate the immunomodulatory capacity of edible mushrooms, including Lepista nuda, Corprinis comatus, Letinus edodes, and Pleurotus eryngii, in mice. BALB/c mice were administered 1, 50, and 500 mg/kg body weight of various mushrooms five times a week over 4 weeks through gastric intubation. The control mice were administered distilled water. No significant changes in body weight were observed. IL-4 and IFN${\gamma}$ production was evaluated with splenic T lymphocytes stimulated in vitro with phytohemagglutinins for 48 hr. The mice group administered L. edodes showed significantly higher ratio of IFN${\gamma}$ versus IL-4 than the other groups. In addition, the ratio of plasma IgG2a versus IgG1 was also significantly elevated in mice treated with L. edodes. However, no significant change was observed in ratio of IgG2a versus IgG1 in splenic B lymphocytes stimulated in vitro with lipopolysaccharides for 7 days. These results indicate that L. edodes can enhance type-1 helper T cell-mediated cellular immunity.