• 대한한의학회지
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• 제21권3호
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• pp.20-30
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• 2000

Objective : This experiment was performed in order to study the effect of an aqueous extract of Salviae radix root(SRRAE) on NO production and NOS gene induction from macrophages Methods : To investigate dose-dependent effects of SRRAE for NO release on the $rIFN-{\gamma}-treated$ macrophages, the cells were incubated for 6 hrs in a medium containing $rIFN-{\gamma}$ (5 U/ml), stimulated with SRRAE and incubated in a CO2 incubator. The cells were treated with 5 U/ml $rIFN-{\gamma}$ plus 100 g/ml of SRRAE, Then, the cells were incubated with various concentrations of NGMMA at $37^{\circ}C$ for 48 hrs, Results : SRRAE had no effect on NO production by itself, whereas recombinant $interferon-{\gamma}(rIFN-{\gamma})$ alone showed modest activity, When SRRAE was used in combination with $rIFN-{\gamma}$, there was a marked cooperative induction of NO production in a dose-dependent manner. The optimal effect of SRRAE on NO production was shown at 6hrs after treatment with $rIFN-{\gamma}$. The SRRAE-induced production of NO was inhibited by NG-monomethyl- L-arginine(NGMMA) and arginase. $rIFN-{\gamma}$ in combination with SRRAE showed a marked increase of the expression of the inducible NOS(iNOS) gene. In addition, the effect of SRRAE was mainly dependent on the SRRAE-induced tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ secretion. Conclusions : SRRAE induces NO production from macrophages as a result of SRRAE-induced $TNF-{\alpha}$ secretion. SRRAE may provide a second signal for synergistic induction of NO production in macrophages already induced to express iNOS gene by $rIFN-{\gamma}$.

• Advances in Traditional Medicine
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• 제1권1호
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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.

• 대한한방내과학회지
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• 제20권1호
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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.

• 대한약리학회지
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• 제31권3호
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• pp.365-375
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• 1995

Anemia-inducing strain of Friend virus (FVA)는 적혈구 progenitor cell의 증식을 촉진하는 생쥐 retrovirus의 일종이다. FVA에 감염된 생쥐는 생성이 촉진된 progenitor cell이 분화되지 못하고 비장내에 축적되므로서 비장비대를 초래한다. 이에 본 실험에서는 FVA에 감염된 생쥐의 비장비대를 지표로 사용하여 2',3'-dideoxycytidine (ddC) 및 $interferon-{\alpha}-A\;(rIFN-{\alpha}-A)$의 항retrovirus효과를 측정하였다. 매일 ddC (100 mg/kg) 및 $rIFN-{\alpha}-A$ (10 KU/mouse)를 각각 단독 또는 병용하여 18일간 복강내 투여시 비장의 비대가 각각 15.1%, 52.7%, 61.6% 억제되었다. 또 다른 실험군으로 ddC를 식수중에 용해하여 (0.1 mg/ml) 경구로 18일간 투여시, 그리고 ddC의 경구투여와 병용하여 $rIFN-{\alpha}-A$을 위와 마찬가지 용량으로 복강내 투여시, 비장비대를 각각 38.4% 및 83.2% 억제하였다. 이 결과는 ddC의 투여시 복강내 주사보다는 경구투여가 더 유효하며, ddC와 $rIFN-{\alpha}-A$는 병용투여시 상가적인 효과가 있음을 제시한다. ddC 투여시 progenitor cell의 특성상 변화를 검토하기 위해, $Ca^{++}$ uptake $[^3H]cyclohexyladenosine$ (CHA) binding 실험을 실시하였다. CHA bindng 실험결과 성숙된 적혈구에서는 저친화성의 결합부위 하나뿐인데 반해, progenitor cell에서는 고친화성과 저친화성의 두가지 결합부위를 나타내었다. $Ca^{++}$ uptake 측정결과 성숙된 적혈구에 비해 대조군의 정상적인progenitor cell은 약 20배 증가를 나타내었으며, ddC를 연속투여한 군에서도 유사한 결과를나타내었다. 이때 CHA에 의한 $Ca^{++}$ uptake의 억제효과를 측정한 바, ddC 100 mg/kg 투여군의 경우 76%로 대조군의 86% 보다 억제효과가 크게 나타났으며, 이들 모두는 adenosine 길항약인 theophylline의 전처치시 대조군과 유사하게 회복되었다.

• 대한한의학회지
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• 제17권2호
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• pp.227-236
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• 1996

The effect of Ligustrum Lucidum(LL) on the production of nitric oxide (NO) and superoxide by murine peritoneal macrophages were investigated. Stimulation of the cells with LL in the presence or absence of interferon-r(IFN-r) resulted in the increased accumulation of nitrite in the medium. To further examine the mechanism of LL induced. NO Synthesis, we evaluated the secretion of tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ by LL in murine macrophages. Treatment of LL increased the secretion of bioactive $TNF-{\alpha}$ in cultured medium. In addition, LL induced NO production was decreased by the treatment of anti-murine $TNF-{\alpha}$. neutralizing antibodies, indicating that LL induced superoxide production was decreased by the treatment of anti-murine $TNF-{\alpha}$ neutralizing antibodies. These data suggested that LL induced superoxide production was related to $TNF-{\alpha}$ secretion. In conclusion, our results indicates that LL may enhance innate immune response and be applied as a immunoregulating drug improving phagocytosis.

• Toxicological Research
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• 제3권1호
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• pp.55-63
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• 1987

A Peri-and Postnatal Study was Carried out to examine the effects of rHuIFN-${\alpha}A$, produced by gene-manipulated E. coli, on offsprings of Wistar rats. The substance was administered intraperitoneally to dams at dose levels of $1{\times}10^5$, $4{\times}10^5$ and $1.2{\times}10^6$ I.U/kg/day during the period from day 17 of gestation to day 21 after delivery. All the pregnant dams were allowed to deliver naturally, and the postnatal development of the offsprings was observed. No noticeable toxic effects and pathological changes on dams were observed, and no detectable variations in postnatal development of offsprings occured.

• 약학회지
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• 제41권3호
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• pp.365-369
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• 1997

Human chorionic gonadotropin (hCG) is a placental hormone and is involved in maintenance of the corpus luteum during pregnancy. In the present study, effect of hCG on nitiric ox ide (NO) generation from peritoneal macrophage was examined. hCG ahd no effect on NO generation by itself, whereas recombinant interferon- ${\gamma}$ (rIFN-${\gamma}$) alone had modest activity. When hCG 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 hCG on NO generation was shown at 6 hr after treatment with rIFN-${\gamma}$. Furthermore, northern blot analysis of showed that hCG increased the expression of inducible NO synthase(iNOS) gene. These results suggest that hCG induces NO generation from macrophages by increasing the expression of iNOS gene.

• 대한한의학회지
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• 제24권2호
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• pp.138-147
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• 2003

Objectives : In this study, we investigated the mechanism by which Chelidonium majus (CM) regulates nitric oxide (NO) production. Methods : Using mouse peritoneal macrophages, the mechanism by which CM regulates NO or tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ production was examined. NO release was measured by the Griess method. $TNF-{\alpha}$ production was measured by the ELISA method. The protein extracts were prepared and samples were analyzed for the inducible NOS(iNOS) expression and nuclear factor kappa $B(NF-{\kappa}B)$ activation by Western blotting. Results : When CM was used in combination with recombinant $interferon-{\gamma}{\;}(rIFN-{\gamma})$, there was a marked cooperative induction of NO production. CM had an effect on NO production by itself. The expression of the iNOS gene was increased in $rIFN-{\gamma}$ plus CM-stimulated peritoneal macrophages and almost completely inhibited by pre-treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of $NF-{\kappa}B$. The $NF-{\kappa}B$ activation was increased in rIFN-{\gamma} plus CM-induced peritoneal macrophages. The increased production of NO from $rIFN-{\gamma}$ plus CM-stimulated peritoneal rnacrophages was decreased by the treatment with $N^{G}-monomethyl-{_L}-arginine{\;}(N^{G}MMA){\;}N^{\alpha}-Tosyl-Phe$ chloromethyl ketone (TPCK) , and was almost completely inhibited by pre-treatment with PDTC. Furthermore, treatment with CM alone or rIFN-{\gamma} plus CM in peritoneal macrophages caused a significant increase in $TNF-{\alpha}$ production. PDTC decreased CM-induced $TNF-{\alpha}$ production significantly. After CM treatment in HT-29 or AGS cells, cell viability decreased. Conclusions : These findings demonstrate that CM increases the production of NO and $TNF-{\alpha}{\;}by{\;}rIFN-{\gamma}-primed$ macrophages and suggest that NF-B plays a critical role in mediating these effects of CM.

• Journal of Periodontal and Implant Science
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• 제24권1호
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• pp.155-164
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• 1994

치조골흡수는 만성치주질환의 전형적인 증상이다. 골흡수에 작용하는 여러 요인들 중에서도, 특히 최근에 들어서 몇몇 cytokine들에 대한 관심이 높아지고 있는데, interleukin-1(IL-1), tumor necrosis factor(TNF) 및 interleukin-6(IL-6) 등이 치주질환의 진행과정에서 중요한 치조골흡수요인으로 제안되고 있다. 본 연구의 목적은 신생쥐의 골조직 배양실험을 통해서 recombinant human $interleukin-1{\beta}$ ($rHuIL-1{\beta}$), recombinant human tumor necrosis $factor-{\alpha}$($rHuTNF-{\alpha}$) 및 recombinant human interleukin-6(rHuIL-6) 의 골흡수 유도효과를 알아보고, cyclooxygenase 억제제인 indomethacin과 recombinant murine $interferon-{\gamma}$($rMurIFN-{\gamma}$)가 이들 cytokine의 골흡수 유도능력에 미치는 영향을 알아봄으로써 이들 cytokine의 작용기구에 대해서 알아보고자 하는데 있다. 생후 1-2일된 쥐에게 $1{\mu}Ci^{45}CaCl_2$를 피하주사하고 4일 후에 쥐를 희생시켜 $^{45}Ca$ 로 표지된 두개골을 얻어 24시간 전배양 후, 각 cytokine ($rHuIL-1{\beta}$, $rHuTNF-{\alpha}$ 및 rHuIL-6)과 cytokine 및 첨가약제 (indomethacin 및 $rMurIFN-{\gamma}$)가 함유된 배지로 교환하여 48시간 배양한다. 골흡수 유도효과는 두개골에서 48시간의 배양 중 유리되는 $^{45}Ca$의 방사능 정도로 평가하였다. 본 연구를 통해 다음과 같은 결과를 얻었다. 1. $rHuIL-1{\beta}$ ($10^{-12}-10^{-9}M$) 및 $rHuTNF-{\alpha}$ ($10^{-10}-10^{-8}M$)는 농도변화에 따르는 골흡수 유도효과를 보였으나 , rHuIL-6 ($10^{-10}-10^{-8}M$)는 유의할 만한 효과를 보이지 않았다. 2. Indomethacin ($10^{-6}M$)은 $rHuIL-1{\beta}$ 및 $rHuTNF-{\alpha}$의 골흡수 유도작용에 유의할 만한 억제효과를 나타내지 않았다. 3. $rMurIFN-{\gamma}$ (1000 U/ml) 은 $rHuIL-1{\beta}$ 및 $rHuTNF-{\alpha}$의 골흡수 유도작용에 유의한 억제효과를 나타내었다. 본연구를 통해 치주질환 환자의 치주조직에서 검출되는 $IL-1{\beta}$ 및 $TNF-{\alpha}$가 치조골 흡수에 중요한 역할을 할 것으로 생각된다.

• Journal of Veterinary Science
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• 제25권1호
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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.