• Title/Summary/Keyword: IRF2

Search Result 75, Processing Time 0.031 seconds

Acrolein with an α,β-unsaturated Carbonyl Group Inhibits LPS-induced Homodimerization of Toll-like Receptor 4

  • Lee, Jeon-Soo;Lee, Joo Young;Lee, Mi Young;Hwang, Daniel H.;Youn, Hyung Sun
    • Molecules and Cells
    • /
    • v.25 no.2
    • /
    • pp.253-257
    • /
    • 2008
  • Acrolein is a highly electrophilic ${\alpha},{\beta}$-unsaturated aldehyde present in a number of environmental sources, especially cigarette smoke. It reacts strongly with the thiol groups of cysteine residues by Michael addition and has been reported to inhibit nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) activation by lipopolysaccharide (LPS). The mechanism by which it inhibits $NF-{\kappa}B$ is not clear. Toll-like receptors (TLRs) play a key role in sensing microbial components and inducing innate immune responses, and LPS-induced dimerization of TLR4 is required for activation of downstream signaling pathways. Thus, dimerization of TLR4 may be one of the first events involved in activating TLR4-mediated signaling pathways. Stimulation of TLR4 by LPS activates both myeloid differential factor 88 (MyD88)- and TIR domain-containing adapter inducing $IFN{\beta}$ (TRIF)-dependent signaling pathways leading to activation of $NF-{\kappa}B$ and IFN-regulatory factor 3 (IRF3). Acrolein inhibited $NF-{\kappa}B$ and IRF3 activation by LPS, but it did not inhibit $NF-{\kappa}B$ or IRF3 activation by MyD88, inhibitor ${\kappa}B$ kinase $(IKK){\beta}$, TRIF, or TNF-receptor-associated factor family member-associated $NF-{\kappa}B$ activator (TANK)-binding kinase 1 (TBK1). Acrolein inhibited LPS-induced dimerization of TLR4, which resulted in the down-regulation of $NF-{\kappa}B$ and IRF3 activation. These results suggest that activation of TLRs and subsequent immune/inflammatory responses induced by endogenous molecules or chronic infection can be modulated by certain chemicals with a structural motif that enables Michael addition.

SAR Image Impulse Response Analysis in Real Clutter Background (실제 클러터 배경에서 SAR 영상 임펄스 응답 특성 분석)

  • Jung, Chul-Ho;Jung, Jae-Hoon;Oh, Tae-Bong;Kwang, Young-Kil
    • Korean Journal of Remote Sensing
    • /
    • v.24 no.2
    • /
    • pp.99-106
    • /
    • 2008
  • A synthetic aperture radar (SAR) system is of great interest in many fields of civil and military applications because of all-weather and luminance free imaging capability. SAR image quality parameters such as spatial resolution, peak to sidelobe ratio (PSLR), and integrated sidelobe ratio (ISLR) can be normally estimated by modeling of impulse response function (IRF) which is obtained from various system design parameters such as altitude, operational frequency, PRF, etc. In modeling of IRF, however, background clutter environment surrounding the IRF is generally neglected. In this paper, analysis method for SAR mage quality is proposed in the real background clutter environment. First of all, SAR raw data of a point scatterer is generated based on various system parameters. Secondly, the generated raw data can be focused to ideal IRF by range Doppler algorithm (RDA). Finally, background clutter obtained from image of currently operating SAR system is applied to IRF. In addition, image quality is precisely analyzed by zooming and interpolation method for effective extraction of IRF, and then the effect of proposed methodology is presented with several simulation results under the assumption of estimation error of Doppler rate.

The inhibitory effect of Scutellaria baicalensis on type 1 interferon production in Raw 264.7 cells (LPS로 자극한 Raw 264.7 cell에서 황금(黃芩)의 type 1 interferon 억제 효과)

  • Kook, Yoon-Bum
    • Herbal Formula Science
    • /
    • v.16 no.2
    • /
    • pp.219-228
    • /
    • 2008
  • Objective : The present study was designed to investigate whether the water extract of the root of Scutellaria baicalensis could regulate lipopolysaccharide (LPS)-induced type 1 interferon. Methods : To evaluate of type 1 interferon inhibitory effect of the root of Scutellaria baicalensis, we examined type 1 interferon in LPS-stimulated RAW264.7 cells. Furthermore, Interleukin (IL)-10 and interferon regulatory factor (IRF) - 1, 7 expression level were examined to study the inhibition mechanisms. Results 1. Extract from the root of Scutellaria baicalensis didn't have any cytotoxity itelf. 2. Extract from the root of Scutellaria baicalensis inhibited interferon-a,b in dose dependant- and type 1 interferon production in time dependant manner. 3. Extract from the root of Scutellaria baicalensis reduced IL-10 and IRF-1, 7 production in LPS-stimulated RAW 264.7 cells. Conclusion : The extract from the root of Scutellaria baicalensis down-regulated LPS-induced type 1 interferon through suppression of IL-10 and IRF-1, 7 expression. This results suggested that the extract from the root of Scutellaria baicalensis may be a beneficial drug against inflammatory diseases.

  • PDF

Development and Implementation of an Over-Temperature Protection System for Power Semiconductor Devices (전력용 반도체 소자의 과열보호시스템 설계 및 구현)

  • Choi, Nak-Gwon;Lee, Sang-Hoon
    • Journal of the Institute of Convergence Signal Processing
    • /
    • v.11 no.2
    • /
    • pp.163-168
    • /
    • 2010
  • This paper presents the practical implementation of an over-temperature protection system for power semiconductor devices. In the proposed system, temperature variation is provided with just using $R_{ds(on)}$ characteristics of power MOSFET, while extra device such as a temperature sensor or an over-temperature detection transistor is needed to monitor the temperature in the conventional method. The proposed protection technique is experimentally tested on IRF840 power MOSFET. The PIC microcontroller PIC16F877A is used for the implementation of the proposed protection algorithm. The built-in 10-bit A/D converter is utilized for detecting voltage variance between a drain and a source of IRF840. The induced temperature-resistance relationship based on the measured drain-source voltage, supplies a gate signal to the power MOSFET. If detected temperature's voltage exceeds any a protection temperature's voltage, the microcontroller removes the trigger signal from the power MOSFET. These test results showed satisfactory performances of the proposed protection system in term of accuracy within 1.5%.

Nonstructural Protein of Severe Fever with Thrombocytopenia Syndrome Phlebovirus Inhibits TBK1 to Evade Interferon-Mediated Response

  • Lee, Jae Kyung;Shin, Ok Sarah
    • Journal of Microbiology and Biotechnology
    • /
    • v.31 no.2
    • /
    • pp.226-232
    • /
    • 2021
  • Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging phlebovirus of the Phenuiviridae family that has been circulating in the following Asian countries: Vietnam, Myanmar, Taiwan, China, Japan, and South Korea. Despite the increasing infection rates and relatively high mortality rate, there is limited information available regarding SFTSV pathogenesis. In addition, there are currently no vaccines or effective antiviral treatments available. Previous reports have shown that SFTSV suppresses the host immune response and its nonstructural proteins (NSs) function as an antagonist of type I interferon (IFN), whose induction is an essential part of the host defense system against viral infections. Given that SFTSV NSs suppress the innate immune response by inhibiting type I IFN, we investigated the mechanism utilized by SFTSV NSs to evade IFNmediated response. Our co-immunoprecipitation data suggest the interactions between NSs and retinoic acid inducible gene-I (RIG-I) or TANK binding kinase 1 (TBK1). Furthermore, confocal analysis indicates the ability of NSs to sequester RIG-I and related downstream molecules in the cytoplasmic structures called inclusion bodies (IBs). NSs are also capable of inhibiting TBK1-interferon regulatory factor 3 (IRF3) interaction, and therefore prevent the phosphorylation and nuclear translocation of IRF3 for the induction of type I IFN. The ability of SFTSV NSs to interact with and sequester TBK1 and IRF3 in IBs demonstrate an effective yet unique method utilized by SFTSV to evade and suppress host immunity.

In vitro antioxidative and anti-inflammatory effects of the compound K-rich fraction BIOGF1K, prepared from Panax ginseng

  • Hossen, Muhammad Jahangir;Hong, Yong Deog;Baek, Kwang-Soo;Yoo, Sulgi;Hong, Yo Han;Kim, Ji Hye;Lee, Jeong-Oog;Kim, Donghyun;Park, Junseong;Cho, Jae Youl
    • Journal of Ginseng Research
    • /
    • v.41 no.1
    • /
    • pp.43-51
    • /
    • 2017
  • Background: BIOGF1K, a compound K-rich fraction prepared from the root of Panax ginseng, is widely used for cosmetic purposes in Korea. We investigated the functional mechanisms of the anti-inflammatory and antioxidative activities of BIOGF1K by discovering target enzymes through various molecular studies. Methods: We explored the inhibitory mechanisms of BIOGF1K using lipopolysaccharide-mediated inflammatory responses, reporter gene assays involving overexpression of toll-like receptor adaptor molecules, and immunoblotting analysis. We used the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay to measure the antioxidative activity. We cotransfected adaptor molecules, including the myeloid differentiation primary response gene 88 (MyD88) and Toll/interleukin-receptor domain containing adaptor molecule-inducing interferon-${\beta}$ (TRIF), to measure the activation of nuclear factor (NF)-${\kappa}B$ and interferon regulatory factor 3 (IRF3). Results: BIOGF1K suppressed lipopolysaccharide-triggered NO release in macrophages as well as DPPH-induced electron-donating activity. It also blocked lipopolysaccharide-induced mRNA levels of interferon-${\beta}$ and inducible nitric oxide synthase. Moreover, BIOGF1K diminished the translocation and activation of IRF3 and NF-${\kappa}B$ (p50 and p65). This extract inhibited the upregulation of NF-${\kappa}B$-linked luciferase activity provoked by phorbal-12-myristate-13 acetate as well as MyD88, TRIF, and inhibitor of ${\kappa}B$ ($I{\kappa}B{\alpha}$) kinase ($IKK{\beta}$), and IRF3-mediated luciferase activity induced by TRIF and TANK-binding kinase 1 (TBK1). Finally, BIOGF1K downregulated the NF-${\kappa}B$ pathway by blocking $IKK{\beta}$ and the IRF3 pathway by inhibiting TBK1, according to reporter gene assays, immunoblotting analysis, and an AKT/$IKK{\beta}$/TBK1 overexpression strategy. Conclusion: Overall, our data suggest that the suppression of $IKK{\beta}$ and TBK1, which mediate transcriptional regulation of NF-${\kappa}B$ and IRF3, respectively, may contribute to the broad-spectrum inhibitory activity of BIOGF1K.

Impulse Response Filtration Technique for the Determination of Phase Velocities from SASW Measurements (SASW시험에 의한 위상속도 결정을 위한 임펄스 응답필터 기법)

  • ;Stokoe, K.H., Il
    • Geotechnical Engineering
    • /
    • v.13 no.1
    • /
    • pp.111-122
    • /
    • 1997
  • The calculation of phase velocities in Spectral-Analysis -of-Surface -Waves (SASW) meas urements requires unwrapping phase angles. In case of layered systems with strong stiffness contrast like a pavement system, conventional phase unwrapping algorithm to add in teger multiples of 2n to the principal value of a phase angle may lead to wrong phase volocities. This is because there is difficulty in counting the number of jumps in the phase spectrum especially at the receiver spacing where the measurements are in the transition Bone of defferent modes. A new phase interpretation scheme, called "Impulse Response Fil traction ( IRF) Technique," is proposed, which is based on the separation of wave groups by the filtration of the impulse response determinded between two receivers. The separation of a wave group is based on the impulse response filtered by using information from Gabor spectrogram, which visualizes the propagation of wave groups at the frequency -time space. The filtered impulse response leads to clear interpretation of phase spectrum, which eliminates difficulty in counting number of jumps in the phase spectrum. Verification of the IRF technique was performed by theoretical simulation of the SASW measurement on a pavement system which complicates wave propagation.opagation.

  • PDF

Expression patterns of innate immunity-related genes in response to polyinosinic:polycytidylic acid (poly[I:C]) stimulation in DF-1 chicken fibroblast cells

  • Jang, Hyun-Jun;Song, Ki-Duk
    • Journal of Animal Science and Technology
    • /
    • v.62 no.3
    • /
    • pp.385-395
    • /
    • 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.

Genetic Analysis of TGFA, MTHFR, and IFR6 in Korean Patients Affected by Nonsyndromic Cleft Lip with or without Cleft Palate (CL/P)

  • Park, Jung-Young;Yoo, Han-Wook;Kim, Young-Ho
    • Genomics & Informatics
    • /
    • v.5 no.2
    • /
    • pp.56-60
    • /
    • 2007
  • Nonsyndromic cleft lip with or without cleft palate (CL/P) is a common craniofacial birth defect that is the result of a mixture of genetic and environmental factors. While studies have identified a number of different candidate genes and loci for the etiology of CL/P, the results have not been consistent among different ethnic groups. To study the genetic association of the candidate genes in Korean patients affected by CL/P, we genotyped 97 nonsyndromic CL/P patients and 100 control individuals using single nucleotide polymorphic markers at the MTHFR, TGFA, and IRF6 genes. We report that the T3827C marker at TGFA showed significant association with nonsyndromic CL/P, but all the other markers tested were not significantly associated with nonsyndromic CL/P in Korean patients.

Genetic heterogeneity of liver cancer stem cells

  • Minjeong Kim;Kwang-Woo Jo;Hyojin Kim;Myoung-Eun Han;Sae-Ock Oh
    • Anatomy and Cell Biology
    • /
    • v.56 no.1
    • /
    • pp.94-108
    • /
    • 2023
  • Cancer cell heterogeneity is a serious problem in the control of tumor progression because it can cause chemoresistance and metastasis. Heterogeneity can be generated by various mechanisms, including genetic evolution of cancer cells, cancer stem cells (CSCs), and niche heterogeneity. Because the genetic heterogeneity of CSCs has been poorly characterized, the genetic mutation status of CSCs was examined using Exome-Seq and RNA-Seq data of liver cancer. Here we show that different surface markers for liver cancer stem cells (LCSCs) showed a unique propensity for genetic mutations. Cluster of differentiation 133 (CD133)-positive cells showed frequent mutations in the IRF2, BAP1, and ERBB3 genes. However, leucine-rich repeat-containing G protein-coupled receptor 5-positive cells showed frequent mutations in the CTNNB1, RELN, and ROBO1 genes. In addition, some genetic mutations were frequently observed irrespective of the surface markers for LCSCs. BAP1 mutations was frequently observed in CD133-, CD24-, CD13-, CD90-, epithelial cell adhesion molecule-, or keratin 19-positive LCSCs. ASXL2, ERBB3, IRF2, TLX3, CPS1, and NFATC2 mutations were observed in more than three types of LCSCs, suggesting that common mechanisms for the development of these LCSCs. The present study provides genetic heterogeneity depending on the surface markers for LCSCs. The genetic heterogeneity of LCSCs should be considered in the development of LCSC-targeting therapeutics.