• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.83-83
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• 1993

생체내 기능조절에 중요한 역할을 하는 prostaglandins(PGs)는 신경계 세포, 순환기계세포, 거삭세포, 섬유아세포 및 암세포 등 여러 부위에 널리 분포되어 있다. 본 연구에서는 PGs생체내 전구체인 arachidonic acid와 구조유사체인 eicosapentaenoic acid(EPA) 및 docosahexaenoic acid(DHA)에 의한 순환기계효과를 TXA$_2$ 생합성과 관련하여 규명하고져 하였다. 또한 여러 가지 면역요법 중 암세포 살해능이 있는 lymphokine activated killer(LAK) 세포의 생성력과 생체내 면역세포 중 암세포의 일차적인 방어작용을 하는 것으로 알려진 natural killer(NK) 세포의 활성도를 PGs생성과 연관시켜 검토하므로써 암환자에 저하되어 있을 면역기구와 PGs와의 상관관계를 규명하고자 하였다.

• Biomolecules & Therapeutics
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• v.4 no.2
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• pp.148-153
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• 1996

Activation of the T lymphocytes results in a variety of early biochemical events ultimately leading to cell proliferation and lymphokine production. Stimulation of the signal transduction cascade in T cells through the T cell receptor coincides with activation of the phosphatidylinositol-phospholipase C (PI-PLC) pathway. Therefore, we have established a model system to screen immune-simulator that can increase the hydrolysis of phosphoinositides in human T cell leukemia Jurkat cells. As a result of screening from herbal medicine extract, 4 extracts (O1ibanum, Ephedrae Herba, Real Gar, Saussureae Radix) were found 14 increase the production of inositol phosphates. All the active fraction from the four kinds of extract were fluted in a different retention time on C-18 HPLC and these active fraction also showed difference in cell specificity. And all the active fractions increased DNA synthesis in T cell. Therefore, it is suggested that the active fraction among 4 extracts might contain a compound having different properties one another.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.104-104
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• 1995

Morphine produces wide-spread immunesuppression, such as lymphokine production, phagocytic activity, natural killer cell activity, cell proliferation, and cell-mediated immunity. On the other hand, one of the representative pharmacological act ions of Panax ginseng is immune enhancement. In this study, we investigated the effects of ginseng total sponin (GTS), and Adaptagen (trade name of ginseng product) on morphine-induced immunesuppression. Morphine hydrochloride (10 mg/kg, sc), GTS (400 mg/kg, oral), Adaptagen (400 mg/kg, oral ) were administered to mice for 14 consecutive days.

• Journal of Life Science
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• v.24 no.10
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• pp.1151-1156
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• 2014

Traditional medicinal plants are widely used to treat many diseases, such as inflammation, infections, and even cancer. Ulmus macrocarpa Hance, a Chinese elm species, is distributed in Korea, China, and Japan. The stem bark is widely employed in Korean traditional medicine to treat dermatitis, mastitis, and edema. The aim of this study was to investigate whether water extract of U. macrocarpa Hance bark (Ulmus cortex) has a immune-modulating function in a mouse model. Three different concentrations (30 mg/kg, 100 mg/kg, and 300 mg/kg) of Ulmus cortex water extract (UCWE) were orally administered to mice for 14 days, and their immune responses were analyzed. Cytokines, such as interleukin (IL)-2, IL-12, and IFN-${\gamma}$, increased in the blood of UCWE-fed groups when compared with a control group. In contrast, the IL-4 level did not change in any of the UCWE-fed groups Cell-mediated cytotoxicity was also assayed using lymphokine-activated killer cells (LAK). LAK showed greater cytotoxicity in the UCWE-fed groups than LAK in the control group. Internal organ indices, such as liver, kidney, spleen, and thymus, were similar in all the groups, including the control group, indicating that UCWE may have been nontoxic in the experimental animals. These data suggest that UCWE has an immune-modulating function in a mouse model.

• Parasites, Hosts and Diseases
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• v.29 no.4
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• pp.381-388
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• 1991

Trichomonas vaginalis is a parasitic nagellate in the urogenital tract of human. Innate cytotonicity of macrophages against T. vaginalis has been recognized, but any report on the cytotoxicity of Iymphokine-activated macrophages to T vaginalis is not yet available. The present study aimed to elucidate the Iymphokine-activated cell mediated cytotoxic effect against T. vaginalis by mouse peritoneal macrophages. Cytotoxicity was measured by counting the release of $^3H-thymidine$ from prelabeled protozoa, and tested in U-bottom microtiter plates. Nitrite concentration in culture supernatants was measured by standard Griess reaction. The results obtained are as follows: 1, The cytotoxicity of macrophages was increased by addition of rIL-2 or $rIFN-{\gamma}$$. 2, Cytotoxicity of macrophages was reduced by addition of rIL-4 to rOM-CSV, rIL-2 or $rIFN-{\gamma}$. 3. Crude Iymphokine mixed with anti-lL-2 decreased the cytotoxity of macrophages. 4. In case of macrophages cultured with $rIFN-{\gamma}$ or rIL-4, the concentration of nitrite was related with cytotokity of macrophages against T. vaginalis, but the cytotoxicity of macrophages cultured with rIL-2 and $rIFN-{\gamma}$ was decreased in spite of its high production of llitrite. From the results obtained, it is assumed that rIL-2 and $rIFN-{\gamma}$ enhance the cytotoxicity of macrophages while rIL-4 inhibits the cytotoxicity against T. vaginalis, and that the production of nitrite does not relate with the cytotoxicity of macrophages, but nitric oxide may play a role as an inhibitory factor on the proliferation of T. vaginalis.

• IMMUNE NETWORK
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• v.1 no.2
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• pp.162-169
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• 2001

Background: Nitric oxide (NO), a cytotoxic molecule is produced in various tissues including tumor cells during interleukin-2 (IL-2) therapy . Lymphokine-activated killer (LAK) cells are induced during IL-2 therapy, and have cytotoxic activity against tumor cells. The current study investigated the effects of NO synthesized in target cells or exposure of target cells to NO on the sensitivity of target cells to LAK cell cytotoxicity. Methods: Cytotoxicity was measured using 4 h chromium release assays. LAK cells which were induced by a 4 day incubation of BALB/c mouse splenocytes with IL-2 (6,000 IU/mL) were employed as effector cells. RD-995 skin tumor cells originated from a C3H/HeN mouse were employed as target cells. NO synthesis in target cells was induced by a 24 h incubation of RD-995 cells with $IFN{\gamma}$ (25 U/mL), TNF (50 U/mL) and IL-1 (20 U/mL). S-nitrosyl acetylpenicillamine (SNAP), an NO donor, was used to expose target cells to NO. $N^G$-monomethyl-L-arginine (MLA) and carboxy-PTIO were added during cytotoxicity assays to inhibit NO synthesis, and to scavenge NO produced by target cells, respectively. Results: Sensitivity of NO-producing RD-995 cells to LAK cell cytotoxicity was decreased by addition of MLA and carboxy-PTIO during cytotoxicity assays. However, the two reagents had no effect on the sensitivity of non-NO-producing RD-995 cells. Pretreatment of RD-995 target cells with SNAP increased the sensitivity in comparison with untreated cells. Conclusions: Sensitivity of target cells to LAK cell cytotoxicity is increased by target cell NO synthesis or exposure to NO. Further studies are needed to evaluate whether these in vitro results have relevance to in vivo phenomena.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7965-7970
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• 2014

One of the goals of tumor immunotherapy is to generate immune cells with potent anti-tumor activity through in vitro techniques using peripheral blood collected from patients. However, cancer patients generally have poor immunological function. Thus using patient T cells, which have reduced in vitro proliferative capabilities and less tumor cell killing activity to generate lymphokine-activated killer (LAK) cells, fails to achieve optimal clinical efficacy. Interleukin-2 (IL-2) is a potent activating cytokine for both T cells and natural killer cells. Thus, this study aimed to identify optimal donors for allogeneic LAK cell immunotherapy based on single nucleotide polymorphisms (SNP) in the IL-2 and IL-2R genes. IL-2 and IL-2R SNPs were analyzed using HRM-PCR. LAK cells were derived from peripheral blood mononuclear cells by culturing with IL-2. The frequency and tumor-killing activity of LAK cells in each group were analyzed by flow cytometry and tumor cell killing assays, respectively. Regarding polymorphisms at IL-2-330 (rs2069762) T/G, LAK cells from GG donors had significantly greater proliferation, tumor-killing activity, and IFN-${\gamma}$ production than LAK cells from TT donors (P<0.05). Regarding polymorphisms at IL-2R rs2104286 A/G, LAK cell proliferation and tumor cell killing were significantly greater in LAK cells from AA donors than GG donors (P<0.05). These data suggest that either IL-2-330(rs2069762)T/G GG donors or IL-2R rs2104286 A/G AA donors are excellent candidates for allogeneic LAK cell immunotherapy.

• Korean Journal of Veterinary Research
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• v.34 no.2
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• pp.307-313
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• 1994

We have previously shown that crude water extract of Euonymus alatus (EA) had strong prophylactic effect against chemically induced-and tumor cell implanted-cancer, and that the mechanisms responsible for its antitumor effects were due to nonspecific enhancement of the NK cell activities and the cell mediated immunity. However, it was unknown that any components of crude extract did work so, since it consisted of several components. In this paper, we fractionated the crude watar EA-extract into several fraction such as hexane-, ethylether-, ethyl acetate-, n-butanol- and water soluble-fraction, and screened the immune regulating activities of each fraction by the evaluation of lymphokine production and activated lymphocyte proliferation. As a result of the component fraction of EA-extract, it was found that n-butanol fraction was a potent immunostimulator, and the remained water soluble fraction also contained some stimulator, But, other fraction did not showed any remarkable effect. It is therefore suggested that EA-glycosides in n-butanol fraction may be new one of the potent biological response modifiers. The present study was also undertaken in an efforts to investigate the effects of elm-bark(EB, Ulmus clavidiana var japonica), which has been used for curing ulcer and inflammation as a folk medicine without any kind of experimental evidence to support this, on the cellular- and humoral-immune responses, lymphocyte function and NK cell activities in mice. Regardless of time and duration of EB-treatment, Arthus reaction and antibody response to SRBC were not modified by EB, but delayed hypersensitivity to SRBC was significantly enhanced only when EB was treated prior to SRBC-sensitization. EB slightly inhibited the proliferation responses of splenocytes to PHA-stimulation, but it significantly augmented the responses of these cells to S aureus Cowan 1 and Con A-activation, and these effects were manifested only when EB was added at culture initiation. EB did not influence Ig secretion of spleen cells but it significantly augmented the Con A-induced 1L 2 and MIF production of splenocytes. NK cell activities of splenocytes were markedly riled when effector cells were pretreated with EB and this augmentation was dine to the increase of binding affinity of effector cells to target cells and the target cell lytic activities of effector cells. These results led to the conclusion that EB triggers increase of cellular immune responses, such as delayed hypersensitivitiy, lymphokine production and NK cell activities. Also these results suggested that EB contains potent immune stimulants, which may provide the rational basis for their therapeutic use as one of the new biological response modifiers.

• Parasites, Hosts and Diseases
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• v.32 no.3
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• pp.185-194
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• 1994

The present study was undertaken to assess the role of cytokines in the activation of peritoneal macrophages from Toxoplasma-infected mice. Peritoneal macrophages from Toxoplasma-infected mice (10 cysts of Beverley strain/mouse) were harvested 8 weeks after infection, and incubated with the mitogen-induced lymphokine, recombinant mouse $interferon-{\gamma}(IFN-{\gamma})$, recombinant mouse tumor necrosis $factor-{\alpha}{\;}(TNF-{\alpha})$ alone or in combination with 4$IFN-{\gamma}(IFN-{\gamma}/TNF-{\alpha})$ for 24hr at 37^{\circ}C$, 5% $CO_2$. Macrophage activation was measured by the amount of $H_20_2{\;}and{\;}N0_2^{-}$ production, and antiToxoplasma activities of macrophages. $IFN-{\gamma}{\;}or{\;}IFN-{\gamma}/TNF-{\alpha}-treated$ macrophages from Toxoplasma-infected mice revealed significantly higher $H_20_2$ production than resident macrophages from Toxoplasma-infected mice. The production of $N0_2^{-}{\;}by{\;}TNF-{\alpha}-,{\;}IFN-{\gamma}-{\;}or{\;}IFN-{\gamma}/TNF-{\alpha}-treated$ macrophages from Toxoplasma-infected mice were significantly higher than that by resident macrophages, whereas lymphokine-treated group produced similar amount as that produced by resident macrophages. Anti-Toxoplasma activities of cytokinetreated macrophages from Toxoplasma-infected mice were Significantly higher than those of resident macrophages. $IFN-{\gamma}-treated$ macrophages were significantly increased production of $H_20_2{\;}and{\;}N0_2^{-}$, and anti-Toxoplasma activities of macrophages between normal and Toxoplasma-infected mice, whereas the other cytokine-treated groups were not significant differences between them. These data suggested that IFN-{\gamma}was the only one of cytokines capable of significantly activating the peritoneal macrophages from Toxoplasmainfected mice.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.18 no.1
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• pp.27-49
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• 2005

당귀음자가감방(當歸飮子加減方)과 외치방(外治方) 병용의 아토피 치료 기전을 규명하고자 NC/Nga 생쥐의 동물 병태 모델을 이용하여 다양한 면역 반응을 관찰하였던 바, 다음과 같은 결론을 얻었다. 1. NC/Nga 생쥐의 피부손상 정도 16주와 20부에 대조군에 비해 36.0%, 37.8% 감소하다. 2. NC/Nga 생쥐의 혈중(血中) IgE, IL-4, IL-5, IL-6, IgM, IgG1 및 IgG2a 수준은 대조군에 비하여 유의성 있게 감소하였고, IL-13 수준은 대조군에 비하여 감소하였으나 유의성을 나타내지 않았다. 반면, $IFN-{\gamma}$ 수준은 유의성 있게 증가하다. 3. NC/Nga 생쥐의 비장 무게는 대조군에 비하여 유의성있게 감소하였다. 4. NC/Nga 생쥐의 lymph node에서 B/f ratio는 증가된 대조군에 비하여 감소하였으며, $CD4^+$와 $CD8^+$ 세포 발현은 대조군에 비하여 증가하였고, $CD4^+$는 유의성있는 감소를, $CD8^+$는 유의성 없는 약간의 증가를 나타내었다. $CD69^+$, CD11a 세포 발현은 대조군에 비하여 유의성있게 감소하였다. 5. NC/Nga 생쥐의 피부조직배양에서 IL-4 IL-5, CCR3 유전자 발현은 대조군에 비하여 현저히 감소하였고, IL-6, IL-13, $CD69^+/CD3{\varepsilon}^+,{\;}CD19^+/CD44^+$ 발현량은 유의성있게 감소하였으며, $IFN-{\gamma}$의 유전자 발현은 대조군에 비하여 증가하였다. 6. NC/Nga 생쥐 귀, 목의 피부 조직 변화에서는 표피와 진피의 염증 정도와 침윤된 염증 면역세포 등이 대조군에 비하여 현저하게 감소되었다. 7. Lymphokine assay에서 IL-4 발현량은 대조군에 비하여 유의성 있게 감소(減少)하였고, $IFN-{\gamma}$의 발현량은 유의성 있게 증가하였다.