• Title/Summary/Keyword: TLR2

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Anti-Inflammatory Activities of Hog Millet (Panicum miliaceum L.) in Murine Macrophages through IRAK-4 Signaling (대식세포에서 IRAK-4신호조절을 통한 기장(Panicum miliaceum L.)의 항염증능에 관한 연구)

  • Park, Mi-Young;Kim, Jae-Hyun;Park, Dong-Sik
    • The Korean Journal of Food And Nutrition
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    • v.24 no.2
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    • pp.268-272
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    • 2011
  • 전곡류의 섭취와 만성질환의 유병율은 음의 상관관계가 있는 것으로 알려져 있다. 본 연구에서는 선행 연구 결과, 지방축적억제능이 우수한 소재로 선정된 기장의 항염증능 여부를 검증하고자 하였다. 이를 위해 RAW264.7 세포에 기장열수분획($1\;{\mu}g/m\ell$$10\;{\mu}g/m\ell$)과 lipopolysaccharide(LPS)를 함께 처리한 후, 24시간 배양시켜 염증매개인자들의 분비량 및 mRNA 발현 정도를 측정하였다. 또한 LPS 자극에 대한 첫 번째 신호전달인자로 알려져 있는 interleukin-1 receptor associated kinase-4(IRAK-4)의 단백질 발현 정도를 측정하였다. 본 연구결과, 기장의 열수분획($10\;{\mu}g/m\ell$)은 LPS로 유도된 NO, $PGE_2$, TNF-${\alpha}$, IL-6 및 MCP-1의 생성량 및 mRNA 발현량을 유의적으로 억제하였다(p<0.05). 특히 이들 지표 중 pro-inflammatory cytokine인 TNF-${\alpha}$와 IL-6의 mRNA 발현량이 효과적으로 감소하였다(p<0.01). IRAK-4의 단백질 발현량 또한 유의적으로 감소하여 LPS 자극에 대한 기장열수분획의 항염증능은 toll-like receptor(TLR)를 통한 IRAK-4를 매개로 하는 신호전달체계 조절에 기인하는 것으로 사료된다.

Lipoteichoic Acid Suppresses Effector T Cells Induced by Staphylococcus aureus-Pulsed Dendritic Cells

  • Son, Young Min;Song, Ki-Duk;Park, Sung-Moo;Han, Seung Hyun;Yun, Cheol-Heui
    • Journal of Microbiology and Biotechnology
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    • v.23 no.7
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    • pp.1023-1030
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    • 2013
  • Lipoteichoic acid (LTA), uniquely expressed on gram-positive bacteria, is recognized by Toll-like receptor 2 (TLR2) on not only antigen-presenting cells but also activated T cells. Therefore, it is reasonable to assume that LTA is acting on T cells. However, little is known about the effect of LTA on T-cell regulation. In the present study, we investigated the immunomodulatory effects of LTA on $CD4^+$ T cells. Effector $CD4^+$ T cells, induced after co-culture with S. aureus-pulsed dendritic cells, produced high levels of interferon-${\gamma}$, CD25, CD69, and TLRs 2 and 4. When effector $CD4^+$ T cells were treated with LTA, the expressions of the membrane-bound form of transforming growth factor (TGF)-${\beta}$ and forkhead box P3 increased. Coincidently, the proliferation of effector $CD4^+$ T cells was declined after LTA treatment. When TGF-${\beta}$ signaling was blocked by the TGF-${\beta}$ receptor 1 kinase inhibitor, LTA failed to suppress the proliferation of effector $CD4^+$ T cells. Therefore, the present results suggest that LTA suppresses the activity of effector $CD4^+$ T cells by enhancing TGF-${\beta}$ production.

The Inhibitory Effect of Fermented Kalopanax pictus by Bioconversion on Endotoxemia and the Competitive Inhibitor Activity on LPS (생물전환을 통한 음나무발효물의 LPS에 대한 경쟁적 억제제 효과 및 내독소혈증 억제 효과)

  • Kim, Sung Phil;Lee, Wha Young;In, Su A;Seong, Eun Young;Kim, Jean Man;Nam, Seok Hyun
    • The Korean Journal of Food And Nutrition
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    • v.32 no.2
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    • pp.106-113
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    • 2019
  • The objective of this study was to evaluate the effect of fermented Kalopanax pictus (KP-F) on macrophage activation and its effect as a competitive inhibitor of LPS and inhibitory effect on endotoxemia. The results showed that KP-F could activate macrophage in a dose-dependent manner, and KP-F was confirmed to act as a ligand for TLR4. Also, it was found that KP-F did not exhibit the same biotoxicity as LPS in intraperitoneal injection, and that it could suppress the neutrophil migration induced by LPS administration. In normal mice, the body weight, tissue weight, and amount of nitrite and pro-inflammatory cytokines in serum showed no significant changes with KP-F diet for 2 weeks, confirming that administration of KP-F in normal mice did not lead to over activation of immune response and biotoxicity. In the mouse model of endotoxemia induced by LPS and D-galactosamine(D-GalN) in sub-lethal dose, the diet of KP-F effectively inhibited the amount of nitrite and cytokines in the blood, and thus was found to be able to relieve the hepatic and kidney injury. In addition, in the endotoxemia mouse model induced by LPS and D-GalN of lethal dose, the survival rate was increased by KP-F diet in a dose-dependent manner.

Development of Non-toxic Recombinant Ricin Vaccine and Evaluation of Vaccine Efficacy (독성을 제거한 재조합 리신 백신 개발 및 효능평가)

  • Hyeongseok Yun;Hae-Eun Joe;Dong Hyun Song;Chi Ho Yu;Young-Jo Song;Gyeung Haeng, Hur
    • Journal of the Korea Institute of Military Science and Technology
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    • v.27 no.2
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    • pp.304-310
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    • 2024
  • Ricin is a highly toxic protein which is produced in the seeds of the castor oil plant. Ricin toxin A chain has ribosomal RNA N-glycosylase activity that irreversibly hydrolyses the N-glycosidic bond of the adenine residue at position 4324 within the 28S rRNA. In this study, we developed non-toxic recombinant ricin vaccine(R51) in E. coli expression system, and evaluated efficacy of the R51 according to adjuvants. When the R51 was administered using aluminum hydroxide as an adjuvant, the vaccine efficacy was higher than that of TLR agonists or aluminum phosphate. Because it is time-consuming to administer the vaccine three times at three-week intervals, we investigated the survival rate and antibody titer of mice according to the change of time interval of vaccination. Interestingly, there was no difference in survival rate and antibody titer when R51 was administered at 0, 1, and 3 weeks or 0, 2, and 4 weeks compared to when administered at 0, 3, and 6 weeks. Therefore, the developed R51 vaccine is promising to protect soldiers from Ricin attack.

Caspase-1 Independent Viral Clearance and Adaptive Immunity Against Mucosal Respiratory Syncytial Virus Infection

  • Shim, Ye Ri;Lee, Heung Kyu
    • IMMUNE NETWORK
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    • v.15 no.2
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    • pp.73-82
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    • 2015
  • Respiratory syncytial virus (RSV) infection is recognized by the innate immune system through Toll like receptors (TLRs) and retinoic acid inducible gene I. These pathways lead to the activation of type I interferons and resistance to infection. In contrast to TLRs, very few studies have examined the role of NOD-like receptors in viral recognition and induction of adaptive immune responses to RSV. Caspase-1 plays an essential role in the immune response via the maturation of the proinflammatory cytokines IL-$1{\beta}$ and IL-18. However, the role of caspase-1 in RSV infection in vivo is unknown. We demonstrate that RSV infection induces IL-$1{\beta}$ secretion and that caspase-1 deficiency in bone marrow derived dendritic cells leads to defective IL-$1{\beta}$ production, while normal RSV viral clearance and T cell responses are observed in caspase-1 deficient mice following respiratory infection with RSV. The frequencies of IFN-${\gamma}$ producing or RSV specific T cells in lungs from caspase-1 deficient mice are not impaired. In addition, we demonstrate that caspase-1 deficient neonatal or young mice also exhibit normal immune responses. Furthermore, we find that IL-1R deficient mice infected with RSV exhibit normal Th1 and cytotoxic T lymphocytes (CTL) immune responses. Collectively, these results demonstrate that in contrast to TLR pathways, caspase-1 might not play a central role in the induction of Th1 and CTL immune responses to RSV.

Nitric Oxide Synthesis is Modulated by 1,25-Dihydroxyvitamin D3 and Interferon-${\gamma}$ in Human Macrophages after Mycobacterial Infection

  • Lee, Ji-Sook;Yang, Chul-Su;Shin, Dong-Min;Yuk, Jae-Min;Son, Ji-Woong;Jo, Eun-Kyeong
    • IMMUNE NETWORK
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    • v.9 no.5
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    • pp.192-202
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    • 2009
  • Background: Little information is available the role of Nitric Oxide (NO) in host defenses during human tuberculosis (TB) infection. We investigated the modulating factor(s) affecting NO synthase (iNOS) induction in human macrophages. Methods: Both iNOS mRNA and protein that regulate the growth of mycobacteria were determined using reverase transcriptase-polymerase chain reaction and western blot analysis. The upstream signaling pathways were further investigated using iNOS specific inhibitors. Results: Here we show that combined treatment with 1,25-dihydroxyvitamin D3 (1,25-D3) and Interferon (IFN)-${\gamma}$ synergistically enhanced NO synthesis and iNOS expression induced by Mycobacterium tuberculosis (MTB) or by its purified protein derivatives in human monocyte-derived macrophages. Both the nuclear factor-${\kappa}B$ and MEK1-ERK1/2 pathways were indispensable in the induction of iNOS expression, as shown in toll like receptor 2 stimulation. Further, the combined treatment with 1,25-D3 and IFN-${\gamma}$ was more potent than either agent alone in the inhibition of intracellular MTB growth. Notably, this enhanced effect was not explained by increased expression of cathelicidin, a known antimycobacterial effector of 1,25-D3. Conclusion: These data support a key role of NO in host defenses against TB and identify novel modulating factors for iNOS induction in human macrophages.

Molecular Mechanism of Macrophage Activation by Exopolysaccharides from Liquid Culture of Lentinus edodes

  • Lee, Ji-Yeon;Kim, Joo-Young;Lee, Yong-Gyu;Rhee, Man-Hee;Hong, Eock-Ki;Cho, Jae-Youl
    • Journal of Microbiology and Biotechnology
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    • v.18 no.2
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    • pp.355-364
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    • 2008
  • Mushrooms are regarded as one of the well-known foods and biopharmaceutical materials with a great deal of interest. ${\beta}$-Glucan is the major component of mushrooms that displays various biological activities such as antidiabetic, anticancer, and antihyperlipidemic effects. In this study, we explored the molecular mechanism of its immunostimulatory potency in immune responses of macrophages, using exopolysaccharides prepared from liquid culture of Lentinus edodes. We found that fraction II (F-II), with large molecular weight protein polysaccharides, is able to strongly upregulate the phenotypic functions of macrophages such as phagocytic uptake, ROS/NO production, cytokine expression, and morphological changes. F-II triggered the nuclear translocation of NF-${\kappa}B$ and activated its upstream signaling cascades such as PI3K/Akt and MAPK pathways, as assessed by their phosphorylation levels. The function-blocking antibodies to dectin-1 and TLR-2, but not CR3, markedly suppressed F-II-mediated NO production. Therefore, our data suggest that mushroom-derived ${\beta}$-glucan may exert its immunostimulating potency via activation of multiple signaling pathways.

A Study on the Relation between Occlusal Wear Area and Occlusal Contact Patterns (교모면적과 교합접촉양태 간의 관계에 대한 연구)

  • Se-Sook Kang;Kyung-Soo Han
    • Journal of Oral Medicine and Pain
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    • v.19 no.2
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    • pp.153-168
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    • 1994
  • The aim of the present study was to investigate a relation between occlusal wear area and occlusal contact patterns. For the purpose, occlusal wear area were measured in 58 dental students and in 129 patients with temporomandibular disorders(TMDs) from dental casts. Teeth used in this study were from canine to second molar on both sides in upper arch, totally ten. Occlusal wear area on casts was marked by pencil and photocopies, and then, the area was measured with planimeter. Occlusal relation was clinically examined with regard to Angle's classification, chewing side preference, lateral guidance pattern and bruxing and/or clenching habit. T-Scan, electronic occlusal contact analyzer, was used to record occlusal contact number, contact force, contact time and occlusal balance that is TLR(total left-right statistics) during tooth contact. All measurement were repeated 3 times and the average value was used for data processing. The obtained results were as follows : 1. Mean value of occlusal wear area did not differ significantly between dental students and patients. 2. There ws not significant difference in wear area between chewing side and non-chewing side in both groups. 3. Occlusal wear area was significantly increased with age in both groups. 4. Three subgroups divided by Angle's classification did not show any difference in occlusal wear area among them, but three subgroups divided by lateral guidance pattern showed slightly significant difference between canine guide subgroup and group function subgroup in patients. Occlusal wear ares\a in group function subgroup wear larger than canine guide subgroup. 5. Mean value of wear area in patients with bruxing and/or clenching habit did not differ from those in patients without such habit. 6. Correlationship among items related to occlusal contact pattern were highly consistent and significant in dental students and only one item significantly correlated with occlusal wear area was tooth contact time.

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Binding model for eriodictyol to Jun-N terminal kinase and its anti-inflammatory signaling pathway

  • Lee, Eunjung;Jeong, Ki-Woong;Shin, Areum;Jin, Bonghwan;Jnawali, Hum Nath;Jun, Bong-Hyun;Lee, Jee-Young;Heo, Yong-Seok;Kim, Yangmee
    • BMB Reports
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    • v.46 no.12
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    • pp.594-599
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    • 2013
  • The anti-inflammatory activity of eriodictyol and its mode of action were investigated. Eriodictyol suppressed tumor necrosis factor (mTNF)-${\alpha}$, inducible nitric oxide synthase (miNOS), interleukin (mIL)-6, macrophage inflammatory protein (mMIP)-1, and mMIP-2 cytokine release in LPS-stimulated macrophages. We found that the anti-inflammatory cascade of eriodictyol is mediated through the Toll-like Receptor (TLR)4/CD14, p38 mitogen-activated protein kinases (MAPK), extracellular-signal-regulated kinase (ERK), Jun-N terminal kinase (JNK), and cyclooxygenase (COX)-2 pathway. Fluorescence quenching and saturation-transfer difference (STD) NMR experiments showed that eriodictyol exhibits good binding affinity to JNK, $8.79{\times}10^5M^{-1}$. Based on a docking study, we propose a model of eriodictyol and JNK binding, in which eriodictyol forms 3 hydrogen bonds with the side chains of Lys55, Met111, and Asp169 in JNK, and in which the hydroxyl groups of the B ring play key roles in binding interactions with JNK. Therefore, eriodictyol may be a potent anti-inflammatory inhibitor of JNK.

Characterization of Proinflammatory Responses and Innate Signaling Activation in Macrophages Infected with Mycobacterium scrofulaceum

  • Kim, Ki-Hye;Kim, Tae-Sung;Lee, Joy G.;Park, Jeong-Kyu;Yang, Miso;Kim, Jin-Man;Jo, Eun-Kyeong;Yuk, Jae-Min
    • IMMUNE NETWORK
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    • v.14 no.6
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    • pp.307-320
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    • 2014
  • Mycobacterium scrofulaceum is an environmental and slow-growing atypical mycobacterium. Emerging evidence suggests that M. scrofulaceum infection is associated with cervical lymphadenitis in children and pulmonary or systemic infections in immunocompromised adults. However, the nature of host innate immune responses to M. scrofulaceum remains unclear. In this study, we examined the innate immune responses in murine bone marrow-derived macrophages (BMDMs) infected with different M. scrofulaceum strains including ATCC type strains and two clinically isolated strains (rough and smooth types). All three strains resulted in the production of proinflammatory cytokines in BMDMs mediated through toll-like receptor-2 and the adaptor MyD88. Activation of MAPKs (extracellular signal-regulated kinase 1/2, and p38, and c-Jun N-terminal kinase) and nuclear receptor (NF)-${\kappa}B$ together with intracellular reactive oxygen species generation were required for the expression of proinflammatory cytokines in BMDMs. In addition, the rough morphotypes of M. scrofulaceum clinical strains induced higher levels of proinflammatory cytokines, MAPK and NF-${\kappa}B$ activation, and ROS production than other strains. When mice were infected with different M. scrofulaceum strains, those infected with the rough strain showed the greatest hepatosplenomegaly, granulomatous lesions, and immune cell infiltration in the lungs. Notably, the bacterial load was higher in mice infected with rough colonies than in mice infected with ATCC or smooth strains. Collectively, these data indicate that rough M. scrofulaceum induces higher inflammatory responses and virulence than ATCC or smooth strains.