• 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 $rIFN-{\gamma}$.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.5025-5030
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• 2015

Immunoregulatory cytokines have an influence on hepatitis C virus (HCV) infection outcome. This study aimed to determine whether single nucleotide polymorphisms (SNP) in IFN- ${\gamma}$ and IL-10 genes are associated with susceptibility and/or are markers of prognosis regarding chronic hepatitis C outcomes. IFN ${\gamma}$ (+874T/A) and IL-10 (-1082G/A) genotypes were determined in 75 HCV genotype 4 patients with different disease severities (chronic hepatitis, n=25, liver cirrhosis and hepatocellular carcinoma (HCC) on top of liver cirrhosis, n=50) and 25 healthy participants using allele-specific polymerase chain reaction. No statistical differences in allele or genotype distributions of IFN ${\gamma}$ and IL-10 genes were detected between patients and controls or between patientgroups. No significant difference in the frequency of IL-10 SNP at position -1082 or IFN-${\gamma}$ at position +874T/A was found between chronic HCV genotype 4 and with progression of disease severity in liver cirrhosis or HCC. In conclusion; interferon-${\gamma}$ and interleukin-10 gene polymorphisms are not predictors of disease progression in patients with chronic hepatitis C (Genotype-4).

• Journal of Periodontal and Implant Science
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• 제30권4호
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• pp.895-913
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• 2000

It is becoming increasingly clear that human gingival fibroblasts(HGF) may play a role in regulating immune responsiveness in inflammatory periodontal lesions. Stimulation of HGF with locally-secreted T cell cytokine $IFN_{\gamma}$ induces human leukocyte antigen class II(HLA II) expression on HGF, which is one of the characteristic feature of professional antigen presenting cells(pAPC). However, $IFN_{\gamma}$-treated HGF and other nonprofessional antigen presenting cells(npAPC) are known to be ineffective or less effective antigen presenter to resting T cells. This study, therefore, was undertaken in an effort to elucidate the differences in expression of cell surface molecules between npAPC in periodontal tissues, such as HGF and periodontal ligament fibroblasts(PDLF), and pAPC such as monocytes/macrophages. Using flow cytometry, the levels of cell surface expression of HLA-D, ICAM-1, LFA-3, and B7-1, which are involved in antigen presentation, were determined in HGF, PDLF and human myelomonocytic cell line THP-1. $IFN_{\gamma}$ clearly induced HLA-D expression on both of fibroblasts and monocytes dose dependently. However, expression level on monocytes were 4 to 5 times higher than that on fibroblasts, and induction rate was faster in monocytes than in fibroblasts. The levels of ICAM-1 expression on fibroblasts and monocytes were enhanced by $IFN_{\gamma}$ in a dose dependent manner. On the other hand, the expression of LFA-3 molecule, which could be detected in fibroblasts and monocytes without cytokine stimulation, was no more enhanced by addition of $IFN_{\gamma}$. B7-1, important costimulatory molecule in T cell activation and proliferation, was not detected on both of fibroblasts and monocytes even when stimulated with $IFN_{\gamma}$, except on monocytes fully differentiated by pretreatment of PMA and treated by $IFN_{\gamma}$. These results suggest that delayed expression of HLA-D and absence of B7-1 on $IFN_{\gamma}$ - treated fibroblasts may at least in part be involved in the ineffectiveness of fibroblasts as primary APC. And it is postulated that although periodontal fibroblasts may not serve as primary APC in normal periodontium, sustained expression of HLA II on ubiquitous fibroblasts in inflammatory lesions may perpetuate immune responses and produce chronic inflammation and tissue injury.

• Archives of Pharmacal Research
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• 제22권3호
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• pp.267-273
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• 1999

In this study we examined the potential for the synergistic augmentation of the antitumor activity of inflammatory mouse peritoneal macrophages by stimulation with protein A combined with $IFN-\gamma$. The moderate augmentative effect induced by preincubation with protein A was demonstrated to be concentration-dependent, whereas IFN-, had a very low activating effect. Following preincubation with both protein A and $IFN-\gamma$, a marked enhancement of macrophage activity was noted. In addition, based on the utilization of neutralizing antibody to TNF-$\alpha$ or the inhibition of NO Production, TNF-$\alpha$ and NO were proven to be involved as mediators during the activation of tumoricidal macrophages by protein A in combination with $IFN-\gamma$. We also demonstrated that supernatants from macrophages treated with protein A plus $IFN-\gamma$ contained both TNF-$\alpha$ and NO at markedly increased levels. Thus, tumor cell lysis in the combined system was mediated via TNF-$\alpha$ or NO. These results demonstrate the synergistic effects on mouse pertioneal macrophage function of protein A in combination with $IFN-\gamma$ and suggest that combinations of such agents may serve as the basis for future in vivo immunotherapy.

• Tuberculosis and Respiratory Diseases
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• 제45권1호
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• pp.36-44
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• 1998

연구배경: IFN-$\gamma$는 단핵식세포를 활성화시키며 여러 종류의 세포내 세균에 대한 숙주의 방어기전에 중요한 역할을 하는 것으로 알려져있다. 그러나 사람에 있어서 IFN-$\gamma$의 항 결핵 효과와 작용기전에 대해서는 거의 알려진 바가 없다. 본 연구에서는 결핵의 발병기전에서 IFN-$\gamma$의 역할을 알아보기 위해 폐포대식세포의 결핵균 탐식과 TNF-$\alpha$ 생산에 IFN-$\gamma$가 미치는 영향을 알아보았다. 방 법: 활동성 폐질환이 없는 8명의 사람에게서 얻은 기관지 폐포세척액에서 폐포대식세포를 표면흡착법으로 분리하여 결핵균과 같이 배양하면서 ($1{\times}10^6$ cells/ml, $3{\times}10^7$ bacteria/ml) 배양액에 IFN-$\gamma$(300U/ml), LPS(0.5ug/ml), 자가혈청(10%)을 첨가하여 2시간 배양 후 항산성 염색(modified Kynion method)을 하여 결핵균을 탐식한 폐포대식세포를 관찰하였다. 그리고 폐포대식세포배양액에 IFN-$\gamma$(300U/ml), MTB($1{\times}106bacteria/ml$) and LPS(0.5ug/ml)를 각각 첨가하여 24시간 배양 후 상층액에서 TNF-$\alpha$의 농도를 ELISA method로 측정하였다. 그리고 IFN-$\gamma$(300U/ml), LPS(0.5ug/ml)로 24시간 자극한 폐포대식세포의 결핵균 탐식율도 관찰하였다. 결 과: IFN-$\gamma$는 폐포대식세포의 결핵균 탐식율을 증가시키지 않았으며(percentage of PAM-phagocytosed MTB: control: $22.1{\pm}4.9$, IFN-$\gamma$: $20.3{\pm}5.3$), 폐포대식세포를 24시간 자극하였을 때 폐포대식세포의 TNF-$\alpha$의 생산을 증가시키지 않았다 (control: $21{\pm}38pg/ml$, IFN-$\gamma$: $87{\pm}106pg/ml$). 그리고 IFN-$\gamma$로 24 시간 전처치한 폐포대식세포의 결핵균 탐식율 또한 증가하지 않았다(control: $24.5{\pm}9.5$, IFN-$\gamma$: $23.4{\pm}10.1$). 결 론: IFN-$\gamma$는 폐포대식세포의 결핵균 탐식과 TNF-$\alpha$ 생산에 영향을 미치지 않는다.

• IMMUNE NETWORK
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• 제14권5호
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• pp.255-259
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• 2014

Physical activity could be considered one of the factors that affect the immune system status and function. To find the relation between exercise and cytokines, we examined the possible effects of an 8-week endurance training program on the serum levels of cytokines, including tumour necrosis factor-alpha (TNF-${\alpha}$) and interferon-gamma (IFN-${\gamma}$) in sedentary men. A total of 30 healthy young male volunteers were randomly divided into an endurance training group and a control group. The training group followed a specific exercise protocol (running on a treadmill for 15~30 min at 50~70% maximal heart rate) for 8 weeks and the control group did not participate in any exercise program. Venous blood samples were collected from both the groups 24 h before and 24 h and 48 h after the exercise. Repeated ANOVA was used for statistical purposes. The serum levels of TNF-${\alpha}$ and IFN-${\gamma}$ were determined by ELISA. Significant (p<0.05) and non-significant (p>0.05) decreases were observed in the serum levels of IFN-${\gamma}$ and TNF-${\alpha}$, respectively, after the 8-week endurance training program. Our findings indicated that an 8-week endurance exercise may affect the serum levels of some inflammatory cytokines, suggesting the beneficial role of this training protocol in elderly population and people with certain conditions (inflammation of the vertebrae or other inflammatory diseases).

• 한국동물위생학회지
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• 제41권2호
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• pp.71-78
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• 2018

Bovine tuberculosis (bTB) is a wide-spread zoonotic disease in cattle, which is casued by Mycobacterium bovis that is a part of Mycobacterium tuberculosis complex (MTC). This study describes a field trial conducted in 42 herds with the history of prevalence bovine tuberculosis. Two cell-mediated immunity tests, the gamma-interferon (${\gamma}-IFN$) assay and the single intradermal tuberculin test (SIT) were applied for the diagnosis of bovine tuberculosis in 5,289 animals. The ${\gamma}-IFN$ assay presented 144 (2.7%) head of cattle with the positive result, and 112 (2.1%) head of cattle were shown to be bTB-positive by the SIT. The positive concordance was 45.5%, and the negative concordance was 98.2%. The ${\gamma}-IFN$ assay showed more positive results in younger cattle, especially between 12 and 23 months of age. It is shown that the strategic combination of both cell-mediated immunity test methods is more efficient for the detection of bTB to reduce the number of false positive individuals which are being slaughtered.

• Tuberculosis and Respiratory Diseases
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• 제59권4호
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• pp.406-412
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• 2005

연구배경 : 최근 말초혈액을 결핵균 특이 항원으로 자극후 분비되는 $IFN-{\gamma}$ 를 측정하는 $QuantiFERON^{(R)}-TB$ Gold (QFT) 와 T $SPOT-TB^{(R)}$(SPOT) 검사가 임상에서 잠복결핵의 진단에 상품화되어 사용되고 있다. 그러나 이전에 시행한 투베르쿨린 검사가 상기 체외 $IFN-{\gamma}$ 검사의 위양성을 유발할 수 있는 가능성에 대해서는 아직 발표된 자료가 없다. 방 법 : 과거 결핵치료력 또는 환자 접촉력이 없는 46명의 15세 남자 고등학생을 대상으로 하였다. 혈액을 채취하여 $IFN-{\gamma}$ 검사를 시행하고, 이단계 TST를 시행하였다. 첫 번째 검사에서 $IFN-{\gamma}$ 검사와 TST가 모두 음성인 학생을 대상으로 하여 2개월 째에 TST, 2개월, 4개월 째에 QFT, 그리고 2개월 째에 SPOT 검사가 반복 시행되었다. 결 과 : TST 경결 크기의 평균값은 $3.1{\pm}5.4mm$ (범위: 0-20)였고, 이단계 TST에서 최종 13/46명(28.3%)이 양성 결과를 나타내었다. SPOT검사는 9명(19.6%)에서 양성이었으며 QFT는 1명(2.2%)에서만 양성이었다. 첫 $IFN-{\gamma}$ 검사와 TST에서 모두 음성인 학생 24명에서 2개월에 시행한 TST 모두 음성이었다. 2개월(23명) 및 4개월(25명)에 시행한 QFT 검사는 모두 음성이었다. 2개월에 SPOT 검사를 시행한 23명 중 1명(4.3%)에서 약양성 결과를 보였다. 결 론 : 두 가지 체외 $IFN-{\gamma}$ 검사의 결과에 일부 차이가 있었으나 2개월 및 4개월 이전에 시행된 TST가 체외 $IFN-{\gamma}$ 검사결과에 영향을 미치지 않음을 알 수 있었다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5513-5518
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• 2013

IFN-${\gamma}$ plays an indirect anti-cancer role through the immune system but may have direct negative effects on cancer cells. It regulates the viability of gastric cancer cells, so we examined whether it affects their proliferation and how that might be brought about. We exposed AGS, HGC-27 and GES-1 gastric cancer cell lines to IFN-${\gamma}$ and found significantly reduced colony formation ability. Flow cytometry revealed no effect of IFN-${\gamma}$ on apoptosis of cell lines and no effect on cell aging as assessed by ${\beta}$-gal staining. Microarray assay revealed that IFN-${\gamma}$ changed the mRNA expression of genes related to the cell cycle and cell proliferation and migration, as well as chemokines and chemokine receptors, and immunity-related genes. Finally, flow cytometry revealed that IFN-${\gamma}$ arrested the cells in the G1/S phase. IFN-${\gamma}$ may slow proliferation of some gastric cancer cells by affecting the cell cycle to play a negative role in the development of gastric cancer.

• Parasites, Hosts and Diseases
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• 제40권3호
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• pp.119-129
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• 2002

Although there are many reports on the splenic (systemic) T cell response after Toxoptasma gondii infection, little information is available regarding the local T cell responses of peritoneal exudate cells (PEC) and gut intraepithelial Iymphocytes (IEL) following peroral infection with bradyzoites. Mice were infected with 40 cysts of the 76K strain of T. gondii, and then sacrificed at days 0, 1, 4, 7 and 10 postinfection (PI). The cellular composition and T cell responses of PEC and IEL were analyzed. The total number of PEC and IEL per mouse increased after infection, but the ratio of increase was higher in IEL. Lymphocytes were the major component of both PEC and IEL. The relative percentages of PEC macrophages and neutrophils/eosinophils increased signiflcantly at day 1 and 4 PI, whereas those of IEL did not change significantly. The percentage of PEC NK1.1 and ${\gamma\delta}T$ cells peaked at day 4 PI (p < 0.0001), and CD4 and $CD8{\alpha}T$ cells increased continuously after infection. The percentages of IEL $CD8{\alpha}$ and ${\gamma\delta}T$ cells decreased slightly at first, and then increased. CD4 and NK1.1 T cells of IEL did not change significantly after infection. $IFN-{\gamma}-producing$ PEC NK1.1 T cells increased significantly from day 1 PI, but the other T cell subsets produced $IFN-{\gamma}$ abundantly thereafter. The proportion of IEL $IFN-{\gamma}-producing$ $CD8{\alpha}$ and ${\gamma\delta}T$ cells increased significantly after infection, while IEL NK1.1 T cells had similar $IFN-{\gamma}$ production patterns. Taken together, CD4 T cells were the major phenotype and the important $IFN-{\gamma}$ producing T cell subsets in PEC after oral infection with T. gondii whereas $CD8{\alpha}T$ cells had these roles in IEL. These results suggest that PEC and IEL comprise different cell differentials and T cell responses, and according to infection route these factors may contribute to the different cellular immune responses.