• 제목/요약/키워드: Toll-like

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IL-l/Toll-like Receptor Superfamily 신호전달에 관여하는 TRAF6 결합 Motif의 규명 (Identification of TRAF6-Binding Motif in IL-1/Toll-like Receptor Superfamily-Mediated Signal Transduction)

  • 임미정
    • 약학회지
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    • 제47권3호
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    • pp.180-183
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    • 2003
  • Crystal structure of TRAF6 in complex with TRAF6-binding sites from CD40 was previously determined. The structure revealed a distinct TRAF6-binding groove of CD40, the key structural determinant of interaction. The structural information leads to a proposed TRAF6-binding motif. This allows the identification of TRAF6-binding sequences in the hIRAK protein, whose functional requirement in IL-1/Toll-like receptor superfamilies-mediated signal transduction is further demonstrated using site-directed mutagenesis. The mutational effects of hIRAK on the down-stream NF-kB signaling shows the importance of the TRAF6 interface for signaling by IL-1/Toll-like receptor superfamilies.

Pichia pastoris로부터 Toll-like Receptor 9의 세포 내 도메인 단백질의 발현과 순수분리 정제 (Expression and Purification of Toll-like Receptor 9 Cytoplasmic Domain in Pichia patoris)

  • 이균영;이곤호
    • Journal of Plant Biotechnology
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    • 제32권4호
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    • pp.269-273
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    • 2005
  • Methylotrophic 효모 Pichia pastoris 발현시스템을 사용하여 인간 TLR9 단백질의 세포내 TIR 도메인을 발현하였다. TIR 단백질이 P. pastoris에서 발현되어 배지 속으로 분비되는 것을 SDS-PAGE로 확인하였고, 발현된 단백질을 western-blot, MALDI-TOF 질량분석으로 동정하였다. 이를 통하여 TIR 딘백질이 P. pastoris에서 안정적으로 발현됨을 알 수 있었다. 그리고 발현된 단백질을 니켈 친화, 양이온교환수지, 겔 투과 크로마토그라피를 사용하여 순수 분리 정제하였다. P. pastoris를 이용한 단백질의 발현과 정제방법은 대장균에서 잘 발현되지 않는 단백질의 발현에 응용될 수 있을 것이다.

Toll-like Receptors in Host Defense and Immune Disorders

  • Lee, Joo-Y.
    • Toxicological Research
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    • 제23권2호
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    • pp.97-105
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    • 2007
  • Toll-like receptors (TLRs) playa crucial role in initiating and regulating innate and adaptive immune responses by detecting invading microbial pathogens. TLRs can also respond to non-microbial molecules derived from damaged tissue. Accumulating evidence suggests that deregulation of TLRs results in the dysfunction of immune system and ultimately increases the risk of many immune and inflammatory diseases including infectious diseases, allergy, and autoimmune diseases. Therefore, understanding how the immune system is controlled by TLRs will provide new insight to find the way to prevent or treat infectious diseases and immune disorders.

지질 다당질 인지경로에서 기질금속단백분해효소-8 분비에 대한 CD14와 Toll-like receptors의 역할 연구 (The role of CD14 and Toll-like receptors on the release of MMP-B in the LPS recognition pathway)

  • 양승민;김태일;설양조;이용무;구영;정종평;한수부;류인철
    • Journal of Periodontal and Implant Science
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    • 제36권3호
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    • pp.579-590
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    • 2006
  • 1. 연구배경 교원질 분해작용을 하는 호중구의 세포질 효소인 기질금속단백분해효소-8은 치주질환, 류마티스 관절염, 그리고 궤양결장염과 같은 염증성 질환에서 농도가 증가한다고 알려져 있다. 최근에는 A. actinomycetemcomitans의 leukotoxin이 사람호중구에서 기질금속단백분해효소-8의 분비를 유도하는 것이 보고되었다. 이 연구의 목적은 선천면역 체계에서 세포표면 항원무리14, Toll-like 수용기, 그리고 $NF-{\kappa}$ B경로를 통하여 A. actinomycetemcomitans의 지질다당질로 유도된 기질금속단백분해효소-8의 분비 여부와 세포기전을 알아보고자 하였다. 2. 연구재료 및 방법 건강한 개인 제공자(남자 13명, 여자 3명)로부터 얻은 개개인의 20ml 말초혈액을 제조사의 지침에 따라 호중구를 추출한 후 항세포표면 항원무리14와 함께 $4^{\circ}C$에서 30분간 전배양 한 후, $37^{\circ}C$에서 9시간 동안 배양시켰다. 추출한 호중구에 Toll-like 수용기 억제제 또는 $NF-{\kappa}$ B억제제인 TPCK를 첨가한 후 $37^{\circ}C$에서 1시간 동안 전배양하고 $37^{\circ}C$에서 9시간 동안 배양시켰다. 호중구에 세포뼈대 억제제인 cholchicine, nocodazole, demecolcine, 그리고 cytochalasin B를 A. actinomycetemcomitans의 지질다당질과 함께 $37^{\circ}C$에서 9시간 동안 배양시켰다. 기질금속단백분해효소-8 분비량은 효소면역측정법을 통해 결정하였다. 통계처리는 일원배치 분산분석법을 이용하였다(p<0.05). 3. 결과 A. actinomycetemcomitans 지질다당질은 기질금속단백분해효소-8의 분비를 증가시켰다. 기질금속단백분해효소-8의 분비는 항세포표면 항원무리14에 의해서 억제되었지만, 항 Toll-like 수용기2, 항 Toll-like 수용기4 항체는 억제시키지 못했다. $NF-{\kappa}$ B 억제제는 A. actinomycetemcomitans의 지질다당질로 유도된 $NF-{\kappa}$ B 결합 활성도와 기질금속단백분해효소-8 분비를 억제하였다. 미세섬유 중합반응 억제제는 A. actinomycetemcomitans의 지질다당질로 유도된 기질금속단백분해효소-8의 분비를 억제시켰으나, 미세관 중합반응억제제는 억제시키지 못했다. 4. 결론 위의 연구결과를 종합하여 볼 때, 기질금속단백분해효소-8은 A. actinomycetemcomitans의 지질다당질로 유도되며, 세포표면 항원무리-$NF-{\kappa}$ B 경로를 통하여 분비되고, 이 분비 과정은 미세섬유 계통이 관여하는 것으로 보인다.

Ligand Recognition by the Toll-like Receptor Family

  • Jin, Mi-Sun;Lee, Jie-Oh
    • Animal cells and systems
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    • 제13권1호
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    • pp.1-8
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    • 2009
  • Toll-like receptor (TLR) family proteins, type I transmembrane proteins, play a central role in human innate immune response by recognizing common structural patterns in diverse molecules from bacteria, viruses and fungi. Recently four structures of the TLR and ligand complexes have been determined by high resolution x-ray crystallographic technique. In this review we summarize reported structures of TLRs and their proposed activation mechanisms. The structures demonstrate that binding of agonistic ligands to the extracellular domains of TLRs induces homo- or heterodimerization of the receptors. Dimerization of the TLR extracellular domains brings their two C-termini into close proximity. This suggests a plausible mechanism of TLR activation: ligand induces dimerization of the extracellular domains, which enforces juxtaposition of intracellular signaling domains for recruitment of intracellular adaptor proteins for signal initiation.

Neonatal innate immunity and Toll-like receptor

  • Yoon, Hye-Sun
    • Clinical and Experimental Pediatrics
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    • 제53권12호
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    • pp.985-988
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    • 2010
  • The innate immune response is the first line of defense against microbial infections. Innate immunity is made up of the surface barrier, cellular immunity and humoral immunity. In newborn, immunologic function and demands are different to adults. Neonatal innate immunity specifically suppresses Th1-type immune responses, and not Th2-type immune responses, which are enhanced. And the impaired response of macrophages is associated with the defective innate immunity in newborn period. Toll-like receptors (TLRs) play a key roles in the detection of invading pathogens and in the induction of innate immune responses. In newborn, the expression of TLRs is age dependent, so preterm has low expression of TLRs. Also, there are defects in signaling pathways downstream of TLRs. As a consequence, the defects of TLRs activity cause the susceptibility to infection in the neonatal period.

The Modulation of Inflammatory Gene Expression by Lipids: Mediation through Toll-like Receptors

  • Lee, Joo Y.;Hwang, Daniel H.
    • Molecules and Cells
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    • 제21권2호
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    • pp.174-185
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    • 2006
  • Toll-like receptors (TLRs) were evolved to detect invading pathogens and to induce innate immune responses in order to mount host defense mechanisms. It becomes apparent that the activation of certain TLRs is also modulated by endogenous molecules including lipid components, fatty acids. Results from epidemiological and animal studies demonstrated that saturated and polyunsaturated dietary fatty acids can differentially modify the risk of development of many chronic diseases. Inflammation is now recognized as an important underlying etiologic condition for the pathogenesis of many chronic diseases. Therefore, if the activation of TLRs and consequent inflammatory and immune responses are differentially modulated by types of lipids in vivo, this would suggest that the risk of the development of chronic inflammatory diseases and the host defense against microbial infection may be modified by the types of dietary fat consumed.

Inhibition of Homodimerization of Toll-like Receptor 4 by 6-Shogaol

  • Ahn, Sang-Il;Lee, Jun-Kyung;Youn, Hyung-Sun
    • Molecules and Cells
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    • 제27권2호
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    • pp.211-215
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    • 2009
  • Toll-like receptors (TLRs) play a critical role in sensing microbial components and inducing innate immune and inflammatory responses by recognizing invading microbial pathogens. Lipopolysaccharide-induced dimerization of TLR4 is required for the activation of downstream signaling pathways including nuclear factor-kappa B ($NF-{\kappa}B$). Therefore, TLR4 dimerization may be an early regulatory event in activating ligand-induced signaling pathways and induction of subsequent immune responses. Here, we report biochemical evidence that 6-shogaol, the most bioactive component of ginger, inhibits lipopolysaccharide-induced dimerization of TLR4 resulting in the inhibition of $NF-{\kappa}B$ activation and the expression of cyclooxygenase-2. Furthermore, we demonstrate that 6-shogaol can directly inhibit TLR-mediated signaling pathways at the receptor level. These results suggest that 6-shogaol can modulate TLR-mediated inflammatory responses, which may influence the risk of chronic inflammatory diseases.

Toll-like receptor and silk sericin for tissue engineering

  • Kim, Seong-Gon;Kweon, HaeYong;Jo, You-Young
    • International Journal of Industrial Entomology and Biomaterials
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    • 제42권1호
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    • pp.1-6
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    • 2021
  • Toll-like receptor (TLR) is responsible for the recognition of foreign protein. Accordingly, TLR is mainly expressed in the immune associated cells. When foreign protein such as silk sericin is considered for the graft, the response of TLR should be considered. TLR is not all or none responsive receptor. TLR can be activated differently by the intensity of the input. Silk sericin is easily fragmented. The protein conformation of silk sericin is different to the degumming method. TLR response to silk sericin may be different to the degumming method. Consequently, objective tailored extraction method should be investigated and developed.

Suppression of the TRIF-Dependent Signaling Pathway of Toll-Like Receptors by Isoliquiritigenin in RAW264.7 Macrophages

  • Park, Se-Jeong;Song, Ho-Yeon;Youn, Hyung-Sun
    • Molecules and Cells
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    • 제28권4호
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    • pp.365-368
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    • 2009
  • Toll-like receptors (TLRs) play an important role in host defense by sensing invading microbial pathogens and initiating innate immune responses. The stimulation of TLRs by microbial components triggers the activation of myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon-${\beta}$ (TRIF)-dependent downstream signaling pathways. Isoliquiritigenin (ILG), an active ingredient of Licorice, has been used for centuries to treat many chronic diseases. ILG inhibits the MyD88-dependent pathway by inhibiting the activity of inhibitor-${\kappa}B$ kinase. However, it is not known whether ILG inhibits the TRIF-dependent pathway. To evaluate the therapeutic potential of ILG, we examined its effect on signal transduction via the TRIF-dependent pathway of TLRs induced by several agonists. ILG inhibited nuclear factor-${\kappa}B$ and interferon regulatory factor 3 activation induced by lipopolysaccharide or polyinosinic-polycytidylic acid. ILG inhibited the lipopolysaccharide-induced phosphorylation of interferon regulatory factor 3 as well as interferon-inducible genes such as interferon inducible protein-10, and regulated activation of normal T-cell expressed and secreted (RANTES). These results suggest that ILG can modulate TRIF-dependent signaling pathways of TLRs, leading to decreased inflammatory gene expression.