• 동의생리병리학회지
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• 제23권5호
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• pp.986-992
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• 2009

Type I interferons (IFNs) are critical mediators of the innate immune system to defend viral infection. Interferon regulatory factor (IRF) and signal transducer and activator of transcription (STAT) play critical roles in type I IFN production in response to viral infection. Luteolin is natural polyphenolic compounds that have anti-inflammatory, cytoprotective and anti-carcinogenic effects. However, the mechanism of action and impact of luteolin on innate immunity is still unknown. In this study, we examined the effects of luteolin on the lipopolysacchride (LPS)-induced inflammatory responses. Luteolin inhibited Type I IFNs expression of mRNA and increased interleukin(IL)-10 expression of mRNA. Next, we examined the protective effects of IL-10 using IL-10 neutralizing antibody (IL-10NA). Blockade of IL-10 action didn't cause a significant reduction of Type I IFNs than LPS-induced luteolin pretreatment. Pretreatment of luteolin inhibited the level of IRF-1, and IRF-7 mRNA and the nuclear translocation of IRF-3. Also, luteolin reduced the activation of STAT - 1, 3. Theses results suggest that luteolin inhibits LPS-induced the production of Type I IFNS by both IRFs and STATs not IL-10 and may be a beneficial drug for the treatment of inflammatory disease.

• Parasites, Hosts and Diseases
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• 제62권1호
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• pp.30-41
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• 2024

The dense granule protein of Toxoplasma gondii, inhibitor of signal transducer and activator of transcription 1 (IST) is an inhibitor of signal transducer and activator of transcription 1 (STAT1) transcriptional activity that binds to STAT1 and regulates the expression of inflammatory molecules in host cells. A sterile inflammatory liver injury in pathological acute liver failures occurs when excessive innate immune function, such as the massive release of IFN-γ and TNF-α, is activated without infection. In relation to inflammatory liver injury, we hypothesized that Toxoplasma gondii inhibitor of STAT1 transcription (TgIST) can inhibit the inflammatory response induced by activating the STAT1/IRF-1 mechanism in liver inflammation. This study used IFN-γ and TNF-α as inflammatory inducers at the cellular level of murine hepatocytes (Hepa-1c1c7) to determine whether TgIST inhibits the STAT1/IRF-1 axis. In stable cells transfected with TgIST, STAT1 expression decreased with a decrease in interferon regulatory factor (IRF)-1 levels. Furthermore, STAT1 inhibition of TgIST resulted in lower levels of NF-κB and COX2, as well as significantly lower levels of class II transactivator (CIITA), iNOS, and chemokines (CLXCL9/10/11). TgIST also significantly reduced the expression of hepatocyte proapoptotic markers (Caspase3/8/9, P53, and BAX), which are linked to sterile inflammatory liver injury. TgIST also reduced the expression of adhesion (ICAM-1 and VCAM-1) and infiltration markers of programmed death-ligand 1 (PD-L1) induced by hepatocyte and tissue damage. TgIST restored the cell apoptosis induced by IFN-γ/TNF-α stimulation. These results suggest that TgIST can inhibit STAT1-mediated inflammatory and apoptotic responses in hepatocytes stimulated with proinflammatory cytokines.

• 한국어병학회지
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• 제18권3호
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• pp.287-292
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• 2005

In the present study, immune gene expression of rainbow trout, Oncorhynchus mykiss, against bacterial endotoxin (LPS) was studied in vivo. The expression of prointflammatory cytokine genes (IL-1$\beta$ and TNF-$\alpha$) and IFN-related genes (IRF-I, Mx-3) at gill was assessed by RT-PCR at different time point of day1 and day 3 post-injection. It was shown that the proinflammatory cytokine gene expression at gill was induced 1 day after LPS injection but the expression was not sustained until day 3. Meanwhile upregulated expression of IFN-related genes was found to be only at day 3 post injection, indicating indirect effect of LPS on these genes.

• 한국약용작물학회:학술대회논문집
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• 한국약용작물학회 2008년도 춘계학술발표회
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• pp.146-147
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• 2008

• Journal of Animal Science and Technology
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• 제62권3호
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• pp.385-395
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• 2020

Polyinosinic:polycytidylic acid (poly[I:C]) can stimulate Toll-like receptor 3 (TLR3) signaling pathways. In this study, DF-1 cells were treated with poly(I:C) at various concentrations and time points to examine the comparative expression patterns of innate immune response genes. The viability of DF-1 cells decreased from 77.41% to 38.68% when cells were treated different dose of poly(I:C) from 0.1 ㎍/mL to 100 ㎍/mL for 24 h respectively. The expressions of TLR3, TLR4, TLR7, TLR15, TLR21, IL1B, and IL10 were increased in dose- and time-dependent manners by poly(I:C) treatment. On the contrary, the expression patterns of interferon regulatory factors 7 (IRF7), Jun proto-oncogene, AP-1 transcription factor subunit (JUN), Nuclear Factor Kappa B Subunit 1 (NF-κB1), and IL8L2 were varied; IRF7 and IL8L2 were increasingly expressed whereas the expressions of JUN and NF-κB1 were decreased in a dose-dependent manner after they were early induced. In time-dependent analysis, IRF7 expression was significantly upregulated from 3 h to 24 h, whereas JUN and NF-κB1 expressions settled down from 6 h to 24 h after poly(I:C) treatment although they were induced at early time from 1 h to 3 h. Poly(I:C) treatment rapidly increased the expression of IL8L2 from 3 h to 6 h with a plateau at 6 h and then the expression of IL8L2 was dramatically decreased until 24 h after poly(I:C) treatment although the expression level was still higher than the non-treated control. These results may provide the basis for understanding host response to viral infection and its mimicry system in chickens.

• 한국지반공학회지:지반
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• 제13권1호
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• pp.111-122
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• 1997

표면파를 이용하여 지반의 강성을 추정하는 기법인 SASW 시험에서 위상속도(phase volocity)를 결정하기 위해서는 위상각(phase angle)의 전개(unwrapping)가 필수적이다. 포장 구조에서처럼 깊이에 따라 강성의 차이가 현저한 경우는 기존의 위상각 전개방식으조는 정확한 위상속도를 결정하기가 용이하지 않다. 이는 기존의 위상각 전개방식은 주위상각(principal phase angle)에 2n의 정수배를 더하는 것인데, 위상각 스펙트럼(phase spectrum)에서 정수배를 결정하는 데에 어려움이 있기 때문이다. 본 연구에서는 이러한 문제점을 해결하기 위해서, 임펄스 응답 필터 기법(Impulse Response Filtration Technique), 또는 IRF기법이라고 하는 새로운 위상각 분석 기법을 제안하였다. IRF 기법의 원리는 임펄스 응답을 필터 처리함으로써 파군(wave group)을 분리하는 것인데,파군의 분리는 임펄스 응답에 대한 Gabor spectrogram을 분석한 정보를 근거로 한다. Gabor spectrogram은 전파되는 파의 에너지를 주파수-시간 공간에서 나타내는 contour 그림으로서, 파군의 전파 상황을 시각적으로 표현하는 수단이다. 이렇게 필터 처리된 임펄스 응답을 이용하면, 위상각 스펙트럼의 분석을 정확하게 할 수 있으며, 위상각의 전개에 있어서 난해함을 제거할 수 있다. 끝으로, 전쳔적인 포장 구조에 대하여 이론적으로 SASW 시험을 모사하였으며, 그 결과를 이용하여 IRF기법의 효용성을 입증하였다.

• 한국동물학회:학술대회논문집
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• 한국동물학회 1999년도 한국생물과학협회 학술발표대회
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• pp.32-32
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• 1999

No Abstract, See Full Text

• BMB Reports
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• 제35권6호
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• pp.583-589
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• 2002

The signal transducer and activator of transcription (STAT)1 is a cytoplasmic-transcription factor that is phosphorylated by Janus kinases (Jak) in response to interferon $\gamma$ (IFN-$\gamma$). The phosphorylated STAT1 translocates to the nucleus, where it turns on specific sets of IFN-$\gamma$-inducible genes, such as the interferon regulatory factor (IRF)-1. We show here that gamma irradiation reduces the IFN-$\gamma$ mRNA expression. The inhibition of the STAT1 phosphorylation and the IRF-1 expression by gamma irradiation was also observed. In contrast, the mRNA levels of IL-5 and transcription factor GATA-3 were slightly induced by gamma irradiation when compared to the non-irradiated sample. Furthermore, we detected the inhibition of cell-mediated immunity by gamma irradiation in the allogenic-mixed lymphocytes' reaction (MLR). These results postulate that gamma irradiation induces the polarized-Th2 response and interferes with STAT1 signals, thereby causing the immunosuppression of the Th1 response.

• Molecular & Cellular Toxicology
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• 제5권3호
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• pp.187-192
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• 2009

Toll-like receptors (TLRs) play an important role in host defense by sensing invading microbial pathogens. The stimulation of TLRs by microbial components triggers the activation of the myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon-$\beta$ (TRIF)-dependent downstream signaling pathways. TLR/MyD88 signaling pathway induces the activation of nuclear factor-kappa B (NF-${\kappa}B$) and the expression of inflammatory cytokine genes, including tumor necrosis factor-alpha, interleukin (IL)-6, IL-12, and IL-$1{\beta}$. On the other hand, TLR/TRIF signaling pathway induces the delayed-activation of NF-${\kappa}B$ and interferon regulatory factor 3 (IRF3), and the expression of type I interferons (IFNs) and IFN-inducible genes. The divalent heavy metal cadmium (Cd) is clearly toxic to most mammalian organ systems, especially the immune system. Yet, the underlying toxic mechanism(s) remain unclear. Cd inhibits the MyD88-dependent pathway by ceasing the activity of inhibitor-${\kappa}B$ kinase. However, it is not known whether Cd inhibits the TRIF-dependent pathway. Presently, Cd inhibited NF-${\kappa}B$ and IRF3 activation induced by lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid. Cd inhibited LPS-induced IRF3 phosphorylation and IFN-inducible genes such as interferon inducible protein-10 and regulated on activation normal T-cell expressed and secreted (RANTES). These results suggest that Cd can modulate TRIF-dependent signaling pathways of TLRs.

• 대한임상검사과학회지
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• 제36권1호
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• pp.27-32
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• 2004

Bone marrow transplantation(BMT) is widely used as curative means of various malignant and nonmalignant hematologic disorders, and early and accurate determination of engraftment is very important for critical management decisions. Reticulocyte counts performed by automated flow cytometric methods is a good indicator of erythropoietic activity and its evaluation has been proposed as an early predictor of bone marrow regeneration. Some reports highlighted the usefulness of the percentage of highly fluorescent reticulocytes and the sum of highly and medium fluorescent reticulocytes(immature reticulocyte fraction, IRF). In Asan Medical Center, the criteria for engraftment following BMT or PBSCT was defined as the first day of a 3-day trend of absolute neutrophil count(ANC)${\geq}500/uL$ and platelet count${\geq}30{\times}10^3/uL$. In 1999, Grotto et al proposed an indidator of bone marrow recovery as the first day on which the IRF was twice the minimum value after bone marrow transplantation. To compare the both criterias, we got consecutive datas of immature reticulocyte fraction, absolute neutrophil count(ANC), WBC count, platelet count and reticulocyte count by XE-2100 automated hematology analyzer(Sysmex Co. Japan) from 33 patients daily after BMT. When compared to standard neutrophil engraftment(10-30 days, $16.2{\pm}4.6days$), IRF engraftment (5-21 days, $11.0{\pm}3.9days$) occured significantly earlier in 87.9% of patients(P<0.05). The mean engraftment day for WBC count(11-29 days, $16.4{\pm}4.3days$) was similar to ANC, but platelet count and reticulocyte count revealed more delayed data (10-49 days, $19.1{\pm}7.4days$ vs 17-64 days, $31.4{\pm}14.1days$). In conclusion, our results confirm that an increase in the immature reticulocyte population is the earliest sign of the hematopoietic recovery after BMT and that automated reticulocyte quantification including immature fraction may be integrated into clinical protocols to evaluate bone marrow reconstitution.