• IMMUNE NETWORK
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• v.23 no.4
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• pp.30.1-30.18
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• 2023

About 0.8 million people die because of hepatitis B virus (HBV) infection each year. In around 5% of infected adults, the immune system is ineffective in countering HBV infection, leading to chronic hepatitis B (CHB). CHB is associated with hepatocellular carcinoma, which can lead to patient death. Unfortunately, although current treatments against CHB allow control of HBV infection, they are unable to achieve complete eradication of the virus. Cytokines of the IFN family represent part of the innate immune system and are key players in virus elimination. IFN secretion induces the expression of interferon stimulated genes, producing proteins that have antiviral properties and that are essential to cell-autonomous immunity. IFN-α is commonly used as a therapeutic approach for CHB. In addition, IFN-γ has been identified as the main IFN family member responsible for HBV eradication during acute infection. In this review, we summarize the key evidence gained from cellular or animal models of HBV replication or infection concerning the potential anti-HBV roles of IFN-γ with a particular focus on some IFN-γ-inducible genes.

• 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.

• IMMUNE NETWORK
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• v.1 no.3
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• pp.250-259
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• 2001

To determine if initial infection with Mycobacterium tuberculosis changes the balance of cytokines between T cells and macrophages, we evaluated interferon (IFN)-${\gamma}$), interleukin-12 (IL)-12, and tumor necrosis factor (TNF)-${\alpha}$ productions by peripheral blood mononuclear cells (PBMC) from 15 untreated active pulmonary tuberculosis (TB) patients and 12 healthy tuberculin reactors (HTR). Freshly isolated PBMC were stimulated with Triton X-100 solubilized protein (TSP), 30-kDa or purified protein derivatives (PPD) antigen for 6, 18 and 96 hours. IL-12 p40 production by antigen-stimulated PBMC from TB patients was significantly decreased compared with that in HTR. In addition, IFN-${\gamma}$ production was significantly depressed in TB patients than that in HTR at a 96-hr stimulation. However, TNF-${\alpha}$ production was significantly higher in antigen-stimulated PBMC from TB than that of HTR. A pronounced increase in IFN-${\gamma}$ protein followed neutralization of IL-10 in early TB patients. However, neutralization of TNF-${\alpha}$ did not significantly alter IFN-${\gamma}$ induction in PBMC from TB patients. There were no significantly differences in the cytokine productions among three proteins, TSP, 30-kDa or PPD antigen. These results indicate that development of TB may be strongly associated with dysregulated productions of IL-12, IFN-${\gamma}$ and TNF-${\alpha}$, during the initial immune responses to M. tuberculosis. Further understanding of operative cytokine networks during human immune cell responses to protein antigens of M. tuberculosis may improve strategies for vaccine development.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3117-3120
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• 2015

Objective: Interferon-${\gamma}$ (IFN-${\gamma}$) and signal transducers and activators of transcription (STATs) each play an important role in carcinogenesis associated with viral infection. Cervical cancer is almost invariably associated with infection by human papillomavirus (HPV), and previous studies suggested that dysregulation of the signal pathway involved in IFN-${\gamma}$ and STATs is associated. Our objective was to evaluate the association of SNPs in STAT2, STAT3, and IFN-${\gamma}$ with cervical cancer susceptibility in Chinese Han women in Hunan province. Materials and Methods: Genomic DNA was extracted from peripheral blood samples of 234 cervical cancer patients and 216 healthy female controls. STAT2 and STAT3 genotyping was performed using polymerase chain reaction-restriction enzyme (PCR-RE) analysis. IFN-${\gamma}$ genotyping was detected by PCR-amplification of specific allele (PASA). Results: For STAT2 rs2066807 polymorphisms, there was no significant difference of genotype distribution (P=0.827) and allele frequencies (P=0.830, OR=1.09, 95% CI: 0.51-2.31) between cases and controls. For STAT3 rs957970 polymorphisms, there was no significant difference of genotype distribution (P=0.455) and allele frequencies (P=0.560, OR=0.92, 95% CI: 0.71-1.20) between cases and controls. For IFN-${\gamma}$ +874A/T polymorphisms, there was no significant difference of genotype distribution (P=0.652) and allele frequencies (P=0.527, OR=1.12, 95% CI: 0.79-1.59) between cases and controls. Conclusion: These results suggest that polymorphisms in STAT2, STAT3 and IFN-${\gamma}$ genes are not likely to be strong predictors of cervical cancer in Han women in southern China.

• Korean Journal of Pharmacognosy
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• v.30 no.3
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• pp.244-249
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• 1999

In order to find less toxic antiviral agents from Basidiomycetes, EA, the water soluble substance, was prepared from the carpophores of Elfvingia applanata(Pers.) Karst. Antiviral activity of EA against vesicular stomatitis virus [Indiana serotype, VSV(IND)] was examined in Vero cells using plaque reduction assay in vitro. And the combined antiviral effects of EA with interferon (IFN) alpha or gamma were examined on the multiplication of VSV(IND). EA caused a concentration-dependent reduction in the plaque formation of VSV(IND) with 50% effective concentration $(EC_{50})$ of $104.02\;{\mu}g/ml$. The results of combination assay were evaluated by the combination index (CI) that was analysed by the multiple drug effect analysis. All cases of the combination of EA with IFN alpha or IFN gamma showed potent synergism with CI values of $0.38{\sim}0.52$ for $50{\sim}90%$ effective levels.

• IMMUNE NETWORK
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• v.2 no.1
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• pp.53-59
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• 2002

Background: Clinical observations and laboratory studies have supported an immune basis for most acquired aplastic anemias, with the majority of patients responding to immunosuppressive therapy. Fas, a member of the tumor necrosis factor (TNF) receptor superfamily is a critical downregulator of cellular immune responses. Proinflammatory cytokines like interferon gamma (IFN-${\gamma}$) and TNF-${\alpha}$ can induce Fas expression and render hematopoietic progenitor cells susceptible to Fas-induced growth suppression and apoptosis. Methods: In order to investigate the involvement of apoptosis in the pathogenesis of aplastic anemia (AA), we measured the expression of Fas antigen and caspase-3 on bone marrow (BM) mononuclear cells (MNCs) of AA in the presence or absence of IFN-${\gamma}$, TNF-${\alpha}$, or macrophage inflammatory protein 1-${\alpha}$ (MIP-$1{\alpha}$). Results: We confirmed that AA BM MNCs were more apoptotic and highly expressed Fas antigen than normal donors. Stimulation by IFN-${\gamma}$, TNF-${\alpha}$, or MIP-$1{\alpha}$ increased Fas antigen and caspase-3 expression in AA BM MNCs than BM MNCs of normal donors. Anti-Fas monoclonal antibody enhanced IFN-${\gamma}$, TNF-${\alpha}$, or MIP$1{\alpha}$ mediated caspase-3 expression in BM MNCs of normal donors. Among these three cytokines, IFN-${\gamma}$ enhanced apoptosis most strongly via Fas-caspase-3 pathway. Conclusion: These results suggest that Fas signal pathway may play a role in the pathophysiology of aplastic anemia and negative hematopoietic regulators like IFN-${\gamma}$ can induce apoptosis of bone marrow progenitors in part by Fas induction.

• The korean journal of orthodontics
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• v.33 no.3 s.98
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• pp.199-210
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• 2003

Tooth movement is the result of bone metabolism in the periodontium, where various cytokines take important roles. Interleukin-6(II-6) and nitrous oxide (NO) were reported to be secreted from osteoblasts in the process of bone resorption. The mechanism of the process has not been clearly understood, but the activation of mitogen-activated protein kinase (MAPK) was known to be an important process in the release of the inflammatory cytotines in macrophages. In this regard, to prove the role of MAPK in the release of IL-6 and NO in MC3T3E-1 osteoblasts, Northern blot analysis, Western blot analysis and immune complex kinase assay were used. As a result, the treatment of MC3T3E-1 osteoblast cultures with combined $interferon-\gamma(IFN-\gamma)$, lipopolysaccharide (LPS) and tumor necrosis $factor-\alpha(TNF-\alpha)$ induces expressions of inducible nitric oxide synthase (iNOS) and IL-6, resulting in sustained releases of large amounts of NO and IL-6. However, $IFN-\gamma,\;LPS,\;and\;TNF-\alpha$ individually induce a non-detectable or small amount of NO and IL-6 in MC3T3E-1 osteoblasts. The role of MAPK activation in the early intracellular signal transduction involved in iNOS and IL-6 transcription in the combined agents-stimulated osteoblasts has been investigated. The p38 MAPK pathway is specifically involved in the combined agents-induced NO and IL-6 release, since NO and IL-6 release in the presence of a specific inhibitor of p38 MAPK, 4-(4-fluorophenyl)-2-(4-metylsulfinylphenyl)-5-(4-metylsulfinylphenyl)-5-(4-pyridyl)imidazole) (SB203580), were significantly diminished. In contrast, PD98059, a specific inhibitor of MEK1, had no effect on NO and IL-6 release. Northern blot analysis showed that the p3a MAPK pathway controlled the iNOS and IL-6 transcription level. These data suggest that p38 MAPK play an important role in the secretion of NO and IL-6 in $LPS/IFN{\gamma}-or\;TNF-\gamma-treated\;MC3T3E-1$ osteoblasts.

• Advances in Traditional Medicine
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• v.6 no.3
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• pp.161-166
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• 2006

Chrysanthemum morifolium (CM) is a herb widely used in medicine for the treatment of a variety of diseases. In this study, using mouse peritoneal macrophages, we have examined whether CM affects nitric oxide (NO), tumor necrosis factor $(TNF)-\alpha$ and interleukin (IL)-6 induced interferon $(IFN)-\gamma$ and lipopolysaccharide (LPS). CM inhibits $IFN-\gamma$ and LPS-induced NO in dose dependent manner. We also found that CM inhibits pro-inflammatory cytokine, $TNF-\alpha$ and IL-6. The expression of cyclooxygenase-2 was reduced by CM. These finding means that CM can be used in controlling macrophages-mediated inflammatory disease.

• YAKHAK HOEJI
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• v.43 no.4
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• pp.464-468
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• 1999

In order to find less toxic antiviral agents from basidiomycetes, EA, the water soluble substance, was isolated from the carpophores of Elfvingia applanata (Pers.) Karst. Anti-encephalomyocarditis (EMC) virus activity of EA was examined in Vero cells by plaque reduction assay in vitro. And the combined antiviral effects of EA with interferon (IFN) alpha and gamma were examined on the multiplication of EMC virus. EA exhibited a concentration-dependent reduction in the plaque formation of EMC virus with 50% effective concentration ($EC_{50}$) of 2.12 mg/ml. The results of combination assay were evaluated by the combination index (CI) that was analysed by the multiple drug effect analysis. The combination of EA with IFN alpha showed potent synergism with CI values of 0.40~0.60 for 50%, 70% and 90% effective levels, but that with IFN gamma showed antagonism with CI values of 2.16~2.83.

• YAKHAK HOEJI
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• v.43 no.4
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• pp.469-473
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• 1999

EA, the water soluble substance, was prepared from the carpophores of Elfvingia applanata (Pers). Karst. Anti-influenza A virus (anti-Flu A) activity of EA was examined of Vero cells by plaque reduction assay in vitro. And the combined antiviral effects fo EA with interferon (IFN) alpha and gamma were examined on the multiplication of Flu A with 50% effective concentration ($EC_50$) of 1.50 mg/ml. The results of combination assay were evaluated by the combination index (CI) that was analysed by the multiple drug effect analysis. The combination of EA with IFN alpha on Flu A showed more potent synergism with CI values of 0.50~0.52 of 50%, 70%, 90% effective levels than that with IFN gamma with CI values of 0.82~0.99.