• Journal of Veterinary Clinics
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• v.14 no.1
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• pp.30-36
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• 1997

It is well estabilished that IL-4, IL-6, $IFN{\gamma}$ and immunoglobulin production are increased as a consequence of advancing age, and endothelial cells increase their expression of pro-inflammatory surface protein, such as ICAM-1, as a consequence of contact with inflammatory cytokines, including IL-1, $TNF{\alpha} or INF{\gamma}.$ This study was designed to define the relationship between age-associated changes of cytokines and immunoglobulin production and ICAM-1 expression in aged mice. Serum from aged mice had elevated IL-6 and immunoglobulin levels compared to mature adult controls and activation-induced production of $IFN{\gamma}$ of splenocytes from aged mice were increased above normal adult level. By immunoperoxidase staining, ICAM-1 in hearts of normal adult mice was expressed occasionally at low levels, but in aged mice, the number of positive blood vessels for ICAM-1 were increased and also the immunoreactivity were stronger. Therefore, these finding indicate that the altered expression of ICAM-1 eith normal aging may actually be correlative to these age-related changes in cytokiness and immunoglobulin production.

• Journal of Periodontal and Implant Science
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• v.25 no.3
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• pp.659-667
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• 1995

파골세포는 조혈기관 단핵의 세포로부터 생성되어 골 홉수에 중요한 역할올 담당하며, 지질다당류는 그람음성균의 세포벽을 이루는 성분으로서 치주질환시 치조골 홉수에 관여한다고 알려져 왔다. 활성화된 림프구, 대식세포와 단핵세포로부터 생성되는 당단백질인 인터페론 감마는 파골세포에 의한 골홉수를 억제한다고 밝혀졌다. 이 연구 논문의 목적은 지질다당류와 인터페론 감마가 닭 골수의 미분화세포가 파골양세포로 전환되는데 어떠한 영향올 주는지를 알아보기 위함이다. 16${\sim}$18 일째의 닭의 배 (chick embryo) 에서 경골을 분리하고 횡절개하여 혈청없는 M-199 배양액에 보관했다. 이것을 9${\mu}m$ filter로 여과시켜서 이미 분화된 파골세포와 기타 다른 분화 세포를 분리했다. 여기에서 파골세포의 전구세포를 얻어 LPS와 IFN-${\gamma}$를 단독 또는 복합처리 하고나서 4일 후에 tartrate resistant acid phosphatase (TRAP) Stain을 시행하고 TRAP 양성이며 핵이 세개 이상인 다핵의 세포형성을 관찰하여 세포를 계수하여 다음과 같은 결과를 얻었다. 1. 닭에서 분리해낸 미분화세포에 0.1. 0.5. 1.0 ${\mu}/ml$ 의 LPS 농도를 처리하고 1 주일간 배양한 결과. 0.1 ${\mu}/ml$ 의 농도에서는 대조군에 비해 TRAP 양성인 파골양세포가 증가하는 경향을 보였으며, 반면에 LPS는 0.5 와 1.0 ${\mu}/ml$ 의 농도에서 세포독성을 보였다.(P<0.05) 2. IFN-${\gamma}$는 50. 500U/ml 의 농도에서 대조군에 비해 TRAP 양성인 파골양세포의 수가 감소하는 경향올 보였다 .3. INF-${\gamma}$는 LPS 에의해 유도된 TRAP 양성인 파골양세포의 형성을 감소시켰고 특히 . 250.500U/ml 의 농도에서 유의 성 있는 감소를 보였다. 위의 결과로부터 LPS는 닭의 골수세포로부터 파골양세포의 형성을 증가시키며 IFN-${\gamma}$는 LPS에의해 유도된 파골양세포수를 감소시킨다는 결론을 얻었다.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1265-1276
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• 1998

Background : Nitric oxide(NO) is an endogenously produced free radical that plays an important role in regulating vascular tone, inhibition of platelet aggregation and white blood cell adhesion to endothelial cells, and host defense against infection. The highly reactive nature of NO with oxygen radicals suggests that it may either promote or reduce oxidant-induced cell injury in several biological pathways. Oxidant injury and interactions between pulmonary vascular endothelium and leukocytes are important in the pathogenesis of acute lung injury, including acute respiratory distress syndrome(ARDS). In ARDS, therapeutic administration of NO is a clinical condition providing exogenous NO in oxidant-induced endothelial injury. The role of exogenous NO from NO donor or the suppression of endogenous NO production was evaluated in oxidant-induced endothelial injury. Method : The oxidant injury in cultured rat lung microvascular endothelial cells(RLMVC) was induced by hydrogen peroxide generated from glucose oxidase(GO). Cell injury was evaluated by $^{51}$chromium($^{51}Cr$) release technique. NO donor, such as S-nitroso-N-acetylpenicillamine(SNAP) or sodium nitroprusside(SNP), was added to the endothelial cells as a source of exogenous NO. Endogenous production of NO was suppressed with N-monomethyl-L-arginine(L-NMMA) which is an NO synthase inhibitor. L-NMMA was also used in increased endogenous NO production induced by combined stimulation with interferon-$\gamma$(INF-$\gamma$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), and lipopolysaccharide(LPS). NO generation from NO donor or from the endothelial cells was evaluated by measuring nitrite concentration. Result : $^{51}Cr$ release was $8.7{\pm}0.5%$ in GO 5 mU/ml, $14.4{\pm}2.9%$ in GO 10 mU/ml, $32.3{\pm}2.9%$ in GO 15 mU/ml, $55.5{\pm}0.3%$ in GO 20 mU/ml and $67.8{\pm}0.9%$ in GO 30 mU/ml ; it was significantly increased in GO 15 mU/ml or higher concentrations when compared with $9.6{\pm}0.7%$ in control(p < 0.05; n=6). L-NMMA(0.5 mM) did not affect the $^{51}Cr$ release by GO. Nitrite concentration was increased to $3.9{\pm}0.3\;{\mu}M$ in culture media of RLMVC treated with INF-$\gamma$ (500 U/ml), TNF-$\alpha$(150 U/ml) and LPS($1\;{\mu}g/ml$) for 24 hours ; it was significantly suppressed by the addition of L-NMMA. The presence of L-NMMA did not affect $^{51}Cr$ release induced by GO in RLMVC pretreated with INF-$\gamma$, TNF-$\alpha$ and LPS. The increase of $^{51}Cr$ release with GO(20 mU/ml) was prevented completely by adding 100 ${\mu}M$ SNAP. But the add of SNP, potassium ferrocyanate or potassium ferricyanate did not protect the oxidant injury. Nitrite accumulation was $23{\pm}1.0\;{\mu}M$ from 100 ${\mu}M$ SNAP at 4 hours in phenol red free Hanks' balanced salt solution. But nitrite was not detectable from SNP upto 1 mM The presence of SNAP did not affect the time dependent generation of hydrogen peroxide by GO in phenol red free Hanks' balanced salt solution. Conclusion : Hydrogen peroxide generated by GO causes oxidant injury in RLMVC. Exogenous NO from NO donor prevents oxidant injury, and the protective effect may be related to the ability to release NO. These results suggest that the exogenous NO may be protective on oxidant injury to the endothelium.

• 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.

• The Journal of Pediatrics of Korean Medicine
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• v.14 no.1
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• pp.79-116
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• 2000

The KGBT has been used to weak children with anorexia, fatigue, and growth retardation. This study was carried out to prove the effects of the hematopoiesis and the immune proliferation by KGBT. Previously, C57BL/6 mice was treated with cyclophosphamide(100mg/kg) for leukopenia, and then administered KGBT (concentration is 1.37 g/kg, 504 mg/kg, and 137 mg/kg) to the treated mice. The mice was analyzed expression of thrombopoietin(TPO), stem cell factor(SCF) and interleukin-3 from bone marrow cell, interleukin-10 (IL-10), and interferon-$ {\gamma}$(INF-${\gamma}$) from splenic cell, and NOSⅡ gene from macrophage using by RT-PCR. Also proliferation of immune cell was analyzed using 3H-thymidine uptake and flow cytometery in splenic cells. The results were obtained as follows ; 1. The total number of WBC, RBC and PLT was increased in the KGBT treated group than in the control group. 2. In vitro, the proliferation of splenic cells was increased in normal, control, and KGBT treated group. And Administration of KGBT was reduced the cytotoxicity by CTX. 3. In bone marrow cell, the gene expression of immune regulatory factor that associated with hematopoiesis, such as TPO, SCF, and IL-13 was increased in the KGBT treated group than control. 4 The titer of hemagglutinin and hemolysin was increased in the KGBT treated group than control. 5. In analysis of positive leucocytes from splenic cell of BALB/c mice, the subpopulation percent of CD4+, CD8+,and CD19+ was increased in the KGBT treated group than control. The KGBT has been used to weak children with anorexia, fatigue, and growth retardation. This study was carried out to prove the effects of the hematopoiesis and the immune proliferation by KGBT. Previously, C57BL/6 mice was treated with cyclophosphamide(100mg/kg) for leukopenia, and then administered KGBT (concentration is 1.37 g/kg, 504 mg/kg, and 137 mg/kg) to the treated mice. The mice was analyzed expression of thrombopoietin(TPO), stem cell factor(SCF) and interleukin-3 from bone marrow cell, interleukin-10 (IL-10), and interferon-$ {\gamma}$(INF-${\gamma}$) from splenic cell, and NOSⅡ gene from macrophage using by RT-PCR. Also proliferation of immune cell was analyzed using 3H-thymidine uptake and flow cytometery in splenic cells. The results were obtained as follows ; 1. The total number of WBC, RBC and PLT was increased in the KGBT treated group than in the control group. 2. In vitro, the proliferation of splenic cells was increased in normal, control, and KGBT treated group. And Administration of KGBT was reduced the cytotoxicity by CTX. 3. In bone marrow cell, the gene expression of immune regulatory factor that associated with hematopoiesis, such as TPO, SCF, and IL-13 was increased in the KGBT treated group than control. 4 The titer of hemagglutinin and hemolysin was increased in the KGBT treated group than control. 5. In analysis of positive leucocytes from splenic cell of BALB/c mice, the subpopulation percent of CD4+, CD8+,and CD19+ was increased in the KGBT treated group than control. 6. The expression of IL-10 gene was reduced in the KGBT treated group than control, whereas the expression of INF-${\gamma}$ was increased in the KGBT treated group. 7. In macrophage, the production of NO and gene expression of NOSH was increased in the KGBT treated group than control. 8. After infection of EMC virus, the survival time of infected mice was longer in the KGBT treated group than control.

• IMMUNE NETWORK
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• v.1 no.3
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• pp.230-235
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• 2001

Background: Finding of the regulation of various gene expression by cytokine including $IFN-{\gamma}$ in hematopoietic stem cell will light up the understanding of pathogenesis of aplastic anemia in various aspects. To study on aplastic anemia, however, we have to circumvent the difficulty of directly obtaining bone marrow stem cells from the patient. Therefore, we tried to find out a cell can replace the bone marrow stem cells for study on cell signaling pathway and regulation of gene expression by $IFN-{\gamma}$. Materials and Methods: HL-60 cells, of 20 ng/mL of $IFN-{\gamma}$. Total RNA was isolated from the cells and RT-PCR of the indoleamine 2,3-dioxygenase (IDO), $IFN-{\gamma}$, TNF-${\alpha}$, $MIP-1{\alpha}$, and $TGF-{\beta}2$ was carried out for the estimation of the gene expression. Results: $IFN-{\gamma}$ induced IDO gene expression of mononuclear cells from umbilical cord blood showed similar pattern as compared to that of bone marrow. Whether $INF-{\gamma}$ was treated or not, $TNF-{\alpha}$ was expressed in both mononuclear cells from umbilical cord blood and bone marrow. However, HL-60 cells showed different expression patterns. HL-60 cells would express neither IDO nor $TNF-{\alpha}$ even under the culture with 20ng/mL of $IFN-{\gamma}$. Conclusion: Our results showed bone marrow can be replaced with mononuclear cells from umbilical cord blood in the study on the relation between aplastic anemia and $IFN-{\gamma}$ including $IFN-{\gamma}$ cell signaling pathway.

• The Journal of Internal Korean Medicine
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• v.38 no.6
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• pp.863-876
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• 2017

Objectives: The aim of this experimental study was to evaluate the anti-neoplastic and anti-inflammatory effects of single and mixed extracts of Ulmus davidiana (UD) and Oldenlandia diffusa (OD) on azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colonic neoplasms in mice. Methods: AOM/DSS induces colitis-associated colonic neoplasms in mice. Mice were divided into seven groups: normal-no inducement and no treatment; control-colonic neoplasms with no treatment; UD-colonic neoplasms and treatment with UD; OD-colonic neoplasms and treatment with OD; UD1+OD1-colonic neoplasms and treatment with UD1 and OD1. UD1+OD2-colonic neoplasms and treatment with UD1 and OD2; UD2+OD1-colonic neoplasms and treatment with UD2 and OD1. Single and mixed preparations of UD and OD were applied to mice for six weeks. The colon length and weight and histopathologic changes of colon tissue were observed. Serum pro-inflammatory cytokines, including tumor necrosis factor-alpha ($TNF-{\alpha}$) and interleukin-6 (IL-6), were determined by enzyme-linked immunosorbent assay. The mRNA expression levels of Bax, Bcl-2, and interferon-gamma ($INF-{\gamma}$) were measured by RT-PCR. Results: The colon length was significantly increased in OD, UD1+OD2, and UD2+OD1 mice, and the colon weight was significantly decreased in OD and UD1+OD2 mice. The morphological change of colon epithelial cells was more suppressed in complex-treatment groups than in single-treatment groups. The inhibitory effect on inflammatory cell invasion was especially shown in UD1+OD2 mice. The serum level of the pro-inflammatory $TNF-{\alpha}$ was decreased in all complex-treatment groups, and the IL-6 level was decreased in UD1+OD1 mice. Single-treatment groups had an increase in the mRNA expression of the pro-apoptosis regulator Bax, and UD2+OD1 decreased the mRNA expression of the anti-apoptosis regulator Bcl-2. The mRNA expression of $INF-{\gamma}$ associated with inflammation was decreased in OD and UD1+OD2 mice. Conclusions: This study suggests that single and mixed extracts of Ulmus davidiana and Oldenlandia diffusa have anti-neoplastic and anti-inflammatory effects on AOM/DSS-induced colonic neoplasms in mice. Therefore, we conclude that UD, OD, and a mixture of UD and OD are potential therapeutic agents for colitis-associated colonic neoplasms.

• Clinical and Experimental Pediatrics
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• v.50 no.11
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• pp.1129-1133
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• 2007

Osteopetrosis, a rare osteosclerotic bone disease characterized by a defect in osteoclast function and the reduced generation of superoxide by leukocytes, can be classified into several types based on their mode of inheritance, age of onset, severity, and associated clinical symptoms. Stem cell transplantation is the only curative therapy for the infantile malignant type, although alternative treatments, such as corticosteroids, calcitriol, and interferon (IFN)-${\gamma}$ have been attempted in patients with milder clinical types. In addition, IFN-${\gamma}$ therapy has been reported to increase bone resorption and hematopoiesis and to improve leukocyte function. Here, we present the cases of two patients with osteopetrosis who benefited from either 3 or 6 years of INF-${\gamma}$ therapy that resulted in improved blood counts and no further pathological fractures.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.23 no.2
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• pp.41-56
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• 2010

Objectives : On an experimental basis, the effects of atopic dermatitis induced materials on the expression of cytokine genes in human monocytes (THP-1, U937) and mast cells were studied. This study was carried out to be considered a fundamental knowledge in the research on the good of oriental medicine. Methods : After culturing THP-1, U937, and HMC-1, with the three different concentrations of LPS ($1\;{\mu}g/ml$), DPE ($10\;{\mu}g/ml$), and DNCB ($1\;{\mu}g/ml$), atopic dermatitis induced materials were treated in the culture medium. To investigate cytokine genes expression patterns, with lysis buffer and separation reagent, total RNA was extracted from THP-1, U937, and HMC-1 at intervals of 0, 12, 24, and 48 hours. Both cytokine mRNA expression patterns by atopic dermatitis induced materials and change of cytokine genes expression patterns in relation to atopy by selenium were analyzed with RT-PCR. Also IL-4 and INF-$\gamma$, which were secreted in the HMC-1, were analyzed using ELISA method. Results : 1. After treating THP-1 and U937 with LPS, DPE, and DNCB, there was no significant change in cytokine genes themselves, but various cytokines (IL-4, IL-6, IL-8, IL-13, IFN-$\gamma$, IFN-a, MCP-1, B2-MG) were expressed. 2. In the case of HMC-1, the expressions of IL-6 and IL-8 were significantly increased in the analysis of mRNA expression by dust mite allergens in DPE. 3. As a result of ELISA method, it is certain that IL-4 and IFN-$\gamma$ protein were secreted in the HMC-1 by DPE. 4. Selenium, an essential trace element, decreased the IL-10 and IL-13 expression in the HMC-1 by DPE. Conclusion : The results suggest that it is necessary to choose proper atopic dermatitis induced materials and suitable cultured cells in establishment of in vitro model of atopic dermatitis.

• Natural Product Sciences
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• v.10 no.6
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• pp.344-346
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• 2004

Eight phenolic compounds (1-8) which were isolated from the barks of Ulmus macrocarpa were evaluated for their inhibitory activities on nitric oxide (NO) and prostagrandin $E_2$ (COX-2) production in $interferon-{\gamma}\;(INF-{\gamma})$ and lipopolysaccharide (LPS)-activated RAW 264.7 cells in vitro. NO and COX-2 levels were moderately reduced by the addition of compounds (1-8). Among them 3,4,5,6,7 and 8 inhibited NO production in a dose dependent manner with an $IC_{50}$ of 92.2, 97.3, 36.1, 43.5, 32.8, 39.4 and 37.1 ${\mu}g/ml$, respectively (positive control, L-NMMA; 36.4 ${\mu}g/ml$), and 3,4,5,6,7 and 8 reduced the COX-2 level in a dose dependent manner with an $IC_{50}$ of 43.2, 24.8, 24.8, 33.4, 44.8 and 22.7 ${\mu}g/ml$, respectively (positive control, indomethacin; 23.4 ${\mu}g/ml$). These results suggest that the phenolic compounds may be developed as potential anti-inflammatory and cancer chemopreventive agents.