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스테로이드의 투여가 말초혈액 단핵구에서 IkB/NF-κB경로에 미치는 영향 (Effect of Steroid Administration Ex Vivo on the IκB/NF-κB Pathway in Human Peripheral Blood Monocytes)

  • 윤호일;이희석;이창훈;이춘택;김영환;한성구;심영수;유철규
    • Tuberculosis and Respiratory Diseases
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    • 제54권5호
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    • pp.542-550
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    • 2003
  • 배경 : 스테로이드는 그 뛰어난 염증억제 효과로 여러 만성 염증성질환의 치료제로 널리 쓰이고 있다. 최근 스테로이드의 염증억제의 기전이 I${\kappa}B$의 전사를 증가시키고, 활성화된 NF-${\kappa}B$를 억제시키는 것으로 밝혀졌다. 그러나 대부분의 연구가 세포주에 스테로이드 처치를 한 후 이루어진 것이어서 본 연구에서는 인체에 직접 스테로이드를 투여한 후, 스테로이드가 NF-${\kappa}B$ 에 미치는 영향을 알아보고자 하였다. 방법 : 건강한 자원자 5명을 대상으로 prednisolone을 0.5mg/kg/d의 용량으로 7일간 투여하였고 투여 전과 후에 각각 말초혈액 단핵구를 추출하여 이를 자극하지 않은 군(baseline), IL-$1{\beta}$, LPS, TNF로 자극한 군으로 나누어 $I{\kappa}B{\alpha}$에 대한 western blot을 시행하였다. 또한 투여 전후에 얻은 말초단핵구를 각각 LPS로 자극하고 EMSA를 시행하였다. 결과 : 5명중 3명에서는 $I{\kappa}B{\alpha}$의 기저발현에 차이가 없었으나, 나머지 2명에서는 스테로이드 투여 후 $I{\kappa}B{\alpha}$의 기저발현이 증가하였다. 5명 모두에서 스테로이드 투여 후에 외부자극에 의한 $I{\kappa}B{\alpha}$의 분해가 억제되었으며, EMSA로 NF-${\kappa}B$의 DNA 결합능이 감소하는 것을 확인하였다. 결론 : 스테로이드의 항염증효과는 $I{\kappa}B{\alpha}$의 기저발현의 증가, NF-${\kappa}B$ 의 DNA 결합능 감소, 그리고 자극 에 의한 $I{\kappa}B{\alpha}$ 분해의 억제에 의한다.

크로스 링크된 단백질 서브시퀀스를 찾는 알고리즘 (Algorithm for identifying cross-linked protein subsequences)

  • 김성권
    • 한국정보과학회논문지:시스템및이론
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    • 제29권9호
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    • pp.514-519
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    • 2002
  • 단백질의 구조를 예측하는 과정에 사용될 수 있는 다음 문제를 고려한다. 길이가 n이고 원소가 모두 양수인 두 배열 A, B와 양수 M이 주어질 때, A[i]+…A[j]+B[k]+…B[ι]=M이 되는 부배열 쌍 A[i]+…A[j],$1{\leq}i{\leq}j{\leq}n$과 B[k], …, B[l], $1{\leq}k{\leq}l{\leq}n$을 모두 찾으시오. 본 논문에서는 이 문제를 $Ο(n^2log n+K)$ 시간에 Ο(n) 메모리를 사용하여 해결하는 알고리즘을 제시한다. 단, K는 찾은 부배열 쌍의 수이다. 기존의 결과는$Ο(n^2log +Klog n)$ 시간과 Ο(n) 메모리였다.

Lipopolysaccharide로 유도된 RAW264.7 세포에서 MAPK에 의한 홍삼추출물의 항염증 효과 (Anti-inflammatory Effect of Red Ginseng through Regulation of MAPK in Lipopolysaccharide-stimulated RAW264.7)

  • 신지수;김종명;안원근
    • 동의생리병리학회지
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    • 제26권3호
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    • pp.293-300
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    • 2012
  • Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are important inflammatory mediators implicated in pathogenesis of inflammation and certain types of human cancers. The present study was designed to determine whether Red Ginseng (RG) could modulate $I{\kappa}B$-kinase, iNOS and COX-2 gene expression and immune responses in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS). RG extract suppressed the expression of LPS-induced $I{\kappa}B$, iNOS, COX-2, and immune responses in a dose-dependent manner. It also showed an anti-inflammatory effect by inhibiting NF-${\kappa}B$ immune response induced by LPS treatment. Inhibitory effect of RG on LPS-induced inflammation was mediated by suppressed phosphorylation of ERK, JNK and p38 through the regulation of the mitogen-activated protein kinase (MAPK) pathway leading to a decreased production of NO, iNOS, COX-2 and NF-${\kappa}B$. The results implied the role of RG as an inflammation regulator and its possible application for curing inflammatory diseases.

금은화의 NF-${\kappa}B$ 활성 억제를 통한 iNOS 조절이 NC/Nga 생쥐의 아토피 피부염에 미치는 영향 (Lonicera Japonica Inhibits Atopy Dermatitis in NC/Nga Mouse through Regulation of iNOS by NF-${\kappa}B$ Suppression)

  • 안상현;김호현
    • 동의생리병리학회지
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    • 제24권2호
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    • pp.278-283
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    • 2010
  • Inducible nitric oxide synthase (iNOS) are important inflammation enzyme and severe up-nitric oxide (NO) production by this enzyme has been intricate with pathogenesis of atopy dermatitis. The present study was designed in order to determine whether Lonicera japonica could inhibit atopy dermatitis through modulation of iNOS by NF-${\kappa}B$ suppression. We found that IKK mRNA and iNOS mRNA expression in RAW 264.7 macrophages stimulated with lipopolysaccharide dose-dependantly decreased by Lonicera japonica (0.4 - 1.0 mg/$m{\ell}$) and NO production decreased. The distribution of NF-${\kappa}B$ p65 and iNOS positive reacted cell in NC/Nga mice with atopy dermatitis were decreased by Lonicera japonica (45 mg/kg/day) and apoptosis were increased. These data likely indicate that Lonicera japonica may act as inflammatory regulator for atopy dermatitis through iNOS modulation by NF-${\kappa}B$B suppression and may be possible to develop useful agent for chemoprevention of NO intricate inflammatory diseases.

Proteasome Inhibitor-Induced IκB/NF-κB Activation is Mediated by Nrf2-Dependent Light Chain 3B Induction in Lung Cancer Cells

  • Lee, Kyoung-Hee;Lee, Jungsil;Woo, Jisu;Lee, Chang-Hoon;Yoo, Chul-Gyu
    • Molecules and Cells
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    • 제41권12호
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    • pp.1008-1015
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    • 2018
  • $I{\kappa}B$, a cytoplasmic inhibitor of nuclear factor-${\kappa}B$ ($NF-{\kappa}B$), is reportedly degraded via the proteasome. However, we recently found that long-term incubation with proteasome inhibitors (PIs) such as PS-341 or MG132 induces $I{\kappa}B{\alpha}$ degradation via an alternative pathway, lysosome, which results in $NF-{\kappa}B$ activation and confers resistance to PI-induced lung cancer cell death. To enhance the anti-cancer efficacy of PIs, elucidation of the regulatory mechanism of PI-induced $I{\kappa}B{\alpha}$ degradation is necessary. Here, we demonstrated that PI up-regulates nuclear factor (erythroid-derived 2)-like 2 (Nrf2) via both de novo protein synthesis and Kelch-like ECH-associated protein 1 (KEAP1) degradation, which is responsible for $I{\kappa}B{\alpha}$ degradation via macroautophagy activation. PIs increased the protein level of light chain 3B (LC3B, macroautophagy marker), but not lysosome-associated membrane protein 2a (Lamp2a, the receptor for chaperone-mediated autophagy) in NCI-H157 and A549 lung cancer cells. Pretreatment with macroautophagy inhibitor or knock-down of LC3B blocked PI-induced $I{\kappa}B{\alpha}$ degradation. PIs up-regulated Nrf2 by increasing its transcription and mediating degradation of KEAP1 (cytoplasmic inhibitor of Nrf2). Overexpression of dominant-negative Nrf2, which lacks an N-terminal transactivating domain, or knock-down of Nrf2 suppressed PI-induced LC3B protein expression and subsequent $I{\kappa}B{\alpha}$ degradation. Thus, blocking of the Nrf2 pathway enhanced PI-induced cell death. These findings suggest that Nrf2-driven induction of LC3B plays an essential role in PI-induced activation of the $I{\kappa}B$/$NF-{\kappa}B$ pathway, which attenuates the anti-tumor efficacy of PIs.

Middle East Respiratory Syndrome Coronavirus-Encoded ORF8b Inhibits RIG-I-Like Receptors by a Differential Mechanism

  • Lee, Jeong Yoon;Kim, Seong-Jun;Myoung, Jinjong
    • Journal of Microbiology and Biotechnology
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    • 제29권12호
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    • pp.2014-2021
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    • 2019
  • Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to the genus Betacoronavirus and causes severe morbidity and mortality in humans especially when infected patients have underlying diseases such as chronic obstructive pulmonary disease (COPD). Previously, we demonstrated that MERS-CoV-encoded ORF8b strongly inhibits MDA5- and RIG-I-mediated induction of the interferon beta (IFN-β) promoter activities. Here, we report that ORF8b seemed to regulate MDA5 or RIG-I differentially as protein levels of MDA5 were significantly down-regulated while those of RIG-I were largely unperturbed. In addition, ORF8b seemed to efficiently suppress phosphorylation of IRF3 at the residues of 386 and 396 in cells transfected with RIG-I while total endogenous levels of IRF3 remained largely unchanged. Furthermore, ORF8b was able to inhibit all forms of RIG-I; full-length, RIG-I-1-734, and RIG-I-1-228, the last of which contains only the CARD domains. Taken together, it is tempting to postulate that ORF8b may interfere with the CARD-CARD interactions between RIG-I and MAVS. Further detailed analysis is required to delineate the mechanisms of how ORF8b inhibits the MDA5/RIG-I receptor signaling pathway.

Inhibition of NF-kB/Rel by Paclitaxel in Mouse Macrophages

  • Lim, Jin-Soo;Lee, Seog-Ki;Jeon, Young-Jin
    • Toxicological Research
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    • 제23권1호
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    • pp.19-24
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    • 2007
  • We demonstrate that paclitaxel, an antitumor agent derived from yew tree, inhibits LPS- and $IFN-{\gamma}$-induced NF-kB/Rel activation in RAW 264.7 cells. Previously, paclitaxel ($>10{\mu}M$) has been known to induce iNOS gene expression in macrophages. However, in the previous report we described that the pretreatment of macrophages with low concentration of paclitaxel ($0.1{\mu}M$) for 8 h inhibited LPS-induced iNOS gene expression. Pretreatment of RAW 264.7 cells with paclitaxel significantly inhibited NF-kB/Rel transcriptional activation. Electrophoretic mobility shift assay further confirmed that pretreatment of macrophages with paclitaxel inhibited NF-kB/Rel DNA binding. Taxotere, a semisynthetic analog of paclitaxel, also inhibited LPS- and $IFN-{\gamma}$-induced iNOS gene expression. Collectively, these series of experiments indicate that paclitaxel inhibits iNOS gene expression by blocking NF-kB/Rel activation.

수정된 equivalent capcity를 이용한 VBR MPEG 비디오 트랙픽의 등가대역폭 계산방법 (Computation method of effective bandwidth of VBR MPEG video traffic using the modified equivalent capacity)

  • 하경봉;이창범;박래홍
    • 전자공학회논문지A
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    • 제33A권10호
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    • pp.40-47
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    • 1996
  • A method for computing effectiv ebandwidth of aggregated varable bit rate (VBR) moving picture experts group (MPEG) video traffic is proposed. To compute statistical characteristics of aggregated MPEG traffic, first we split input MPEG traffic into I, B, and P frame traffics and aggregate respective I, B, and P frame traffics according to the frame type. Second statisticsal characteristics of the aggregated MPEG traffic are obtained using those of aggregated I, B, and P frame traffics. The effective bandwidth of the aggregated I frame traffic is computed by using the gaussian bound. Using the modified equivalent capacity, we obtain the effective bandwidths of aggregated B and P frame traffics and then compute the effective bandwidth of the combined B and P frame traffic. Finally the effective bandwidth of the aggregated MPEG traffic is computed by adding the gaussian bound of the aggregated I frame traffic and modifed equivalent capacity of combined B and P frame traffic. Computer simulation shows that the proposed method estimates effective bandwidth of the aggregated MPEG traffic well.

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삼국시대 심엽형 귀걸이 양식에 대한 연구 (A Study on the Heat shaped Earring in the Period of the Three States)

  • 김문자
    • 복식
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    • 제45권
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    • pp.29-40
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    • 1999
  • The purpose of this study is to classify of the Heart shaped Earring in old tombs of Three Kingdom States. First Heart shaped Earring is 7 part in according to heart styles. I-A type was original style and that was influenced by scythe style. I-A II-A type was general style that was found in most of the old tombs in Kokuryo Pacijae ancient Silla Gaya. I-B II-2-A type was also found in most of the old tombs except Kokuryo. Then II-2-A type was transmitted to Japanese Heart shaped Earring. I-A, I-B, II-1, II-2-A type was general style in ancient Silla gaya. Ii-1-B, II-2-B. II-3-A type was excavated from the only Pacjae tombs and II-3-B type was excavated from Kokuryo tombs. II-3-A, II-3-B type was unique style that was found in old tombs in Kokuryo, Pacjae.

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$Bi_2$$O_3$첨가량이 Pb($Zr_{0.54}$, $Ti_{0.46}$)$O_3$의 유전, 압전특성에 미치는 영향 (Effects of $Bi_2$$O_3$ additions on the dielectric and piezoelectric properties in Pb($Zr_{0.54}$, $Ti_{0.46}$)$O_3$)

  • 배이열;서동수
    • E2M - 전기 전자와 첨단 소재
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    • 제6권3호
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    • pp.207-213
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    • 1993
  • Pb(Z $r_{0.54}$, $Ti_{0.46}$) $O_{3}$에 B $i_{2}$ $O_{3}$를 0.0wt%까지 첨가하여 미세구조, 유전, 압전, 성질에 미치는 영향을 고찰하였다. B $i_{2}$ $O_{3}$의 고용범위는 약 0.5~0.7wt%정도 이었고 B $i_{2}$ $O_{3}$ 첨가량이 증가함에 따라서 결정립의 크기가 감소하였다. B $i_{2}$ $O_{3}$첨가량이 증가함에 따라 고용한계까지는 $d_{33}$ , tan .delta., .xi.$_{r}$(분극후)값이 증가하였으며 Qm값과 밀도는 감소하였다. $K_{p}$ 값은 B $i^{3+}$ 가 P $b^{2+}$를 치환하므로 형성되는 Pb공공의 형성에 의해 자발분극이 증가됨에 따라 증가하였다.다.

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