• Toxicological Research
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• v.3 no.1
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• pp.45-53
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• 1987

A teratogenicity study was carried out on Sprague-Dawley rats which have been given the intravenously or intraperitonealy injections of rHuIFN-${\alpha}$A, an available therapeutic agent, at dose levels of $1{\times}10^5$, $4{\times}10^5$ and $1.2{\times}10^6$ I.U/kg/day for a period of 11 days from day 7 to day 17 of gestation. Two-thirds of the pregnant females in each group were sacrificed on day 20 of gestation and their fetuses were examined. The remaining dams were allowed to litter naturally, and the postnatal development of the off springs was observed. No changes were observed in all aspects of parameters between the treated and the control dams. The incidence of external, internal, and skeletal anomalies were not significantly increased in the fetuses of any treated groups. The rHuIFN-${\alpha}A$ caused no effects on parturition, lactation, and postnatal growth.

• Advances in Traditional Medicine
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• v.1 no.1
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• pp.71-81
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• 2000

High molecular weight water-insoluble chitosan alone has been previously shown to exhibit in vitro stimulatory effect on macrophages nitric oxide (NO) production. However, high molecular weight water-soluble chitosan (WSC) had no effect on NO production by itself. When WSC was used in combination with recombinant $interferon-{\gamma}\;(Rifn-{\gamma})$, there was a marked cooperative induction of NO synthesis in a dose-dependent manner. The optimal effect of WSC on NO synthesis was shown at 24 h after treatment with $rIFN-{\gamma}$. The increased production of NO from $rIFN-{\gamma}$ plus WSC-stimulated RAW 264.7 macrophages was decreased by the treatment with $N^G$ $monomethyl-_L-arginine$. The increase in NO synthesis was reflected, as an increased amounts of inducible NO synthase (iNOS) protein. Synergy between $rIFN-{\gamma}$ and WSC was mainly dependent on WSC-induced nuclear $factor-_KB$ activation. The present results indicate that WSC may provide various activities such as anti-microbial, anti-tumoral, and anti-viral. In addition, since NO has emerged as an important intracellular and intercellular regulatory molecule having functions as diverse as vasodilation, neural communication, cell growth regulation and host defense, it is tempting to hypothesize that this WSC is involved in the local control of the various fundamental processes such as cardiagra, cardiac infarction, impotence etc.

• The Journal of Internal Korean Medicine
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• v.20 no.1
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• pp.143-152
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• 1999

Dansam, the root of Salvia miltiorrhiza Bge, (Labiatae), has a bitter taste and a slightly 'cold' property, and is nontoxic. In the present study, effect of Dansam on nitric oxide (NO) generation from peritoneal macrophags was examined. Dansam had no effect on NO generation by itself, whereas recombinant interferon-${\gamma}\;(rIFN-{\gamma})$ alone had modest activity. When Dansam was used in combination with $rIFN-{\gamma}$, there was a marked cooperative induction of NO generation in a dose-dependent manner, The optimal effect of Dansam on NO generation was shown at 6 hr after treatment with $rIFN-{\gamma}$. Furthermore, the effect of Dansam was mainly dependent on Dansam-induced tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$ secretion. These results suggest that Dansam induces NO generation from macrophages by the result of Dansam-induced $TNF-{\alpha}$ secretion.

• The Journal of Internal Korean Medicine
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• v.20 no.1
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• pp.73-82
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• 1999

Nitric oxide (NO) is now recognized as a mediator of several biological and immunological functions, but unlike classical neurotransmitters. NO simply diffuse of the postsynaptic cells and around affecting cells. Taraxacum officinale (Compositae) has been used for maintenance of vitality, and they still occupy an important place in the traditional Korean medicine. We have examined that the effect of Taraxacum officinale water extract on NO synthesis in microglial cells of murine's brain, using the Griess method. And this study was evident that Taraxacum officinale did not induce NO production without recombinant interferon gamma ($rIFN-{\gamma}$), whereas Taraxacum officinale (10-1000 g/ml) with $rIFN-{\gamma}$ effectively produced NO in microglial cells of brain. As result. NO production in microglial cells increased most significantly in dose of 100 g/ml of the Taraxacum officinale and the production of NO was dependent on the dose of Taraxacum officinale, NG-monomethyl-L-arginine, competitive inhibitor of NO synthase, reduced the NO production by Taraxacum officinale stimulation with $rIFN-{\gamma}$ in microglial cells of murine. The effect of Taraxacum officinale was mainly dependent on Taraxacum officinale-induced tumor necrosis factor- secretion. Conclusively, this study suggested that Taraxacum officinale stimulate NO production at microglial cells in brain, which may be an important factor for mediating immune and neuroendocrinologic regulation in nervous system.

• Journal of Veterinary Science
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• v.25 no.1
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• pp.11.1-11.16
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• 2024

Background: Canine parvoviral enteritis (CPE) is a fatal disease worldwide. The treatment of CPE is based mainly on supportive and symptomatic treatment. Antiviral addition to the treatment may result in a higher survival. Objectives: This study evaluated the effects of antiviral treatments with a standardized treatment (ST) on the clinical and inflammatory response of dogs with naturally occurring CPE. Methods: Twenty-eight dogs with CPE caused by canine parvovirus type 2 were divided randomly into treatment groups. The ST group received fluid, antibiotic, antiemetic, and deworming treatments. The antiviral treatment groups received the same ST with an additional antiviral drug, recombinant feline interferon omega (rFeIFN-ω), oseltamivir (OSEL) or famciclovir (FAM). Results: Compared to the healthy control, the tumor necrosis factor-α, interleukin-1β, interferon (IFN)-α, IFN-γ, haptoglobin, and C-reactive protein values were high (p < 0.05) on day zero. At presentation, mild lymphopenia, neutropenia, and a high neutrophil to lymphocyte (LYM) ratio (NLR) were also observed. Adding rFeIFN-ω to the ST produced the best improvement in the clinical score with a decreased NLR, while leucocytes remained low and inflammatory markers stayed high on day three. The survival rates of the groups were 85.7% in ST+IFN, 71.4% in ST+OSEL, 71.4% in ST+FAM, and 57.1% in ST groups on day seven. Conclusions: Antiviral drugs may be valuable in treating CPE to improve the clinical signs and survival. In addition, the decrease in NLR in favor of LYM may be an indicator of the early prognosis before the improvement of leukocytes, cytokines, and acute phase proteins in CPE.

• Parasites, Hosts and Diseases
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• v.35 no.3
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• pp.189-196
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• 1997

The purpose of this study is to determine whether nitric oxide is involved in the extracellular killing of Trichomoncs uasinalis by mouse (BALB/c) peritoneal macrophages and RAW264.7 cells activated with LPS or rIFN-γ and also to observe the effects of various chemicals which affect the production of reactive nitrogen intermediates (RNl) in the cytotoxicity against T. vnginnlis. The cytotoxicity was measured by counting the release of (3H)-thymidine from labelled protozoa and NOa was assayed by Griess reaction. Nemonomethyl-L-arginine (L-NMHA), Nenitro-L-arginine methyl ester (NAME) and arginase inhibited cytotoxicity to T. vaginnlis and nitrite production by activated mouse perioneal macrophagrs and RAW 264.7 cells. The addition of excess L-arginine competitively restored trichomonacidal activity of macrophages. Exogenous addition of FeSO4 inhibited cytotoxicity to T. vaginaLis and nitric products of macrophages. From above results, it is assumed that nitric oxide plays an important role in the host defense mechanism of macrophages against T ucfinalis.

• The Journal of Internal Korean Medicine
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• v.25 no.2
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• pp.245-257
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• 2004

This study was done to evaluate the antiallergic effects of Naenghyohwan(NHH). Cytotoxic activity for lung fibroblast cells, cytokines transcript expression of IL-1, IL-4, IL-5, TNF-${\alpha}$, IL-6, IL-10, TGF-${\beta}$1, IFN-${\gamma}$, production of IL-4, IL-10. IFN-${\gamma}$, IgE in anti-CD40mAb plus rIL-4 stimulated murine splenic B cells and the production of histamin released in mast cells, and the expression of histamine release factor(HRF) in splenic B cells were measurd. The following results were obtained. NHH did not showed cytotoxicity in fibroblast cells. NHH increased the gene synthesis of TNF-${\alpha}$, IFN-${\gamma}$(m-RNA). NHH decreased the gene synthesis of IL-1${\beta}$, IL-4, IL-5, IL-6, TGF-${\beta}1$(m-RNA). NHH decreased the appearance of IL-4, IgE significantly. NHH increased the appearance of IL-10. IFN-${\gamma}$ significantly. NHH decreased the proliferation of B cells significantly. NHH decreased the appearance of histamin expression of HRF in mast cells significantly. The results suggest NHH is effective against the allergies. Continued studies of the antiallergic effects of NHH are urged.

• Proceedings of the Korea Society of Poultry Science Conference
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• 1999.11a
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• pp.34-50
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• 1999

A cDNA encoding chicken interferon-gamma (chIFN-${\gamma}$) was amplified from P34, a CD4$^{+}$ T-cell hybridoma by reverse transcription-polymerase chain reaction (RT-PCR) and cloned into pUC18. THe sequences of cloned PCR products were determined to confirm the correct cloning. Using this cDNA as probe, chicken genomic library from White Leghorn spleen was screened. Phage clones harboring chicken interferon-gamma (chIFN-${\gamma}$) were isolated and their genomic structure elucidated. The chIFN-${\gamma}$ contains 4 exons and 3 introns spanning over 14 kb, and follows the GT/AG rule for correct splicing at the exon/intron boundaries. The four exons encode 41, 26, 57 and 40 amino acids, respectively, suggesting that the overall structure of IFN-${\gamma}$ is evolutionairly conserved in mammalian and avian species. The 5’-untranslated region and signal sequences are located in exon 1. Several AT-rich sequences located in the fourth exon may indicate a role in mRNA turnover. The 5’-flanking region contains sequences homologous to the potential binding sites for the mammalian transcription factors, activator protein-1(AP-1) activator protein-2(AP-2) cAMP-response element binding protein(CREB), activating transcription factor(ATF), GATA-binding fator(GATA), upstream stimulating factor(USF), This suggests that the mechanisms underlying transcriptional regulation of chicken and mammalian IFN-${\gamma}$ genes may be similar.r.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.6
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• pp.1479-1486
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• 2003

In order to evaluate the antiallergic effects of Kamiohihyosan(KCHS), studies were done. We measured the cytotoxic activity for lung fibroblast cell, cytokines transcript expression, production of IL-4, IL-10, IFN-γ, proliferation of B cell in anti-CD40mAb plus rIL-4 stimulated murine splenic B cells. The results were obtained as follows: KCHS was not showed cytotoxicity in the fibroblast lung cell, KCHS increased the gene synthesis of INF-γ, TNF-α, IL1-β, IL-6, IL-10(m-RNA), KCHS decreased the gene synthesis of IL-4, IL-5, TGF-β(m-RNA), KCHS decreased the appearance of IL-4, IgE significantly, KCHS increased the appearance of IL-10, IFN-γ significantly, KCHS decreased the proliferation of B cell significantly, The facts above prove that KCHS is effective against the allergy. Thus, I think that we should study on this continuously.

• Clinical and Experimental Pediatrics
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• v.46 no.7
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• pp.702-709
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• 2003

Purpose : $IFN{\gamma}$ sentitizes many tumor cells to $TNF{\alpha}$ and FASL-mediated apoptosis by enhancing the expression of TNF or FAS/CD95 receptor and modulating the activation of caspase and Bcl-2 family. It has been reported that $IFN{\gamma}$ and $TNF{\alpha}$ synergistically caused differentiation and growth inhibition of neuroblastoma cells. Even though some neuroblastoma cell express FASR/FASL on the cell surface, they could not induce apoptosis by ligation of the FAS/CD95 receptor. But the treatment of $IFN{\gamma}$ is reported to induce apoptosis in some neuroblastoma cell lines through the CD95/CD95L autocrine circuit. In this study, we examined whether $IFN{\gamma}$ could affect $TNF{\alpha}$ and agonistic FAS/CD95 antibody(CH-11)-induced apoptosis against neuroblastoma cell lines that had shown diverse drug sensitivity and resistance. Methods : CHLA-15, CHLA-90 and LA-N-2 neuroblastoma cells were cultured in IMDM and treated with recombinant $IFN{\gamma}$, $TNF{\alpha}$ and CH-11 antibody. Cell viability was measured by DIMSCAN with a fluorescent calcein-AM. Apoptosis was analyzed through flow cytometry using Annexin V-PE and 7-ADD staining and confirmed by pancaspase and caspase-8 blocking experiments. The expression of TNF RI and FAS/CD95 receptor was evaluated by flow cytometry using the corresponding antibody and PE-conjugated secondary antibody. Results : $IFN{\gamma}$ or $TNF{\alpha}$ alone had no demonstrable cytotoxic effects, whereas both cytokines in combination induced apoptosis synergistically in CHLA-15 and CHLA-90 cells. Although there was no cytotoxicity with the ligation of CH-11 alone in CHLA-90 cells, pretreatment of $IFN{\gamma}$ increased the sensitivity of CH-11-mediated apoptosis. The expression of TNFRI and FAS/CD95R were non-specifically enhanced after treatment of $IFN{\gamma}$ without relation to sensitivity to $TNF{\alpha}$ and CH-11. This finding suggest up-regulation of both receptors may contribute to sensitization of $TNF{\alpha}$ and CH-11-mediated apoptosis by $IFN{\gamma}$ in only sensitive cell lines. Conclusion : $IFN{\gamma}$ induced sensitization of $TNF{\alpha}$ and agonistic FAS/CD95 antibody-mediated apoptosis on some neuroblastoma cells through up-regulation of TNFRI and FAS/CD95 receptor.