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Rhus Verniciflua Stokes Extract Suppresses Expression of Metalloproteinases, iNOS and COX-2 in THP-1 Cells Via Inhibiting NF-𝜅B and MAPK Phosphorylation

  • Ko, Hwanjoo;Jang, Eungyeong;Kim, Youngchul
    • The Journal of Korean Medicine
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    • v.41 no.4
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    • pp.12-26
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    • 2020
  • Objectives: The aim of this study is to investigate the mechanisms involved in the anti-inflammatory and anti-tumor effects of Rhus verniciflua Stokes (RVS) on PMA-differentiated human monocytic leukemia THP-1 cells. Methods: Cells were treated with various concentrations of RVS decoction (0-300㎍/ml) for 24, 48, and 72h. Cell viability was evaluated by MTS/PMS assay. The expressions of MMP-2, MMP-9, TIMP-1, TIMP-2, iNOS and COX-2 mRNA and proteins were measured using RT-PCR and western blotting, respectively. Results: RVS suppressed expression of MMP-2 and MMP-9 mRNA. It also down-regulated iNOS and COX-2 mRNA and protein expression. RVS inhibited NF-𝜅B p65 activity and the phosphorylation of Akt and MAPK (ERK and p38 MAPK). Instead, the phosphorylation of JNK is increased at a very low concentration but decreased at higher concentrations. Conclusion: RVS is regarded to inhibit the expression of MMP and TIMP as well as iNOS and COX-2 gene expression via directly inhibiting the activation of NF-𝜅B and phosphorylation of MAPK pathway in THP-1 cells. This suggests RVS have potential to be used as a therapeutic agent for acute myeloid leukemia (AML).

Astaxanthin Ameliorates Atopic Dermatitis by Inhibiting the Expression of Signal Molecule NF-kB and Inflammatory Genes in Mice

  • Donghwan, Kim;Yong-Suk, Kim;Ho Sueb, Song
    • Journal of Acupuncture Research
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    • v.39 no.4
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    • pp.304-309
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    • 2022
  • Background: This study was conducted to determine the anti-inflammatory effect of astaxanthin, on atopic dermatitis. Methods: Changes in mouse body weight, lymph node weight, and the degree of improvement in symptoms were measured to determine the inflammatory response. Real-time reverse transcription-polymerase chain reaction tests were performed to determine the degree of expression of inflammation-related cytokines (IL-31 and IL-33 and chemokines such as CCL17 and CCL22), and western blot analysis was performed to evaluate the expression of inflammation-related factors (iNOS, COX-2, and NF-kB signaling molecules p-IkBα, p50, p-65 and pSTAT3). Results: The degree of symptoms significantly improved in the PA+AX group. Lymph node weight in the PA+AX group was lower than the PA group. Inflammatory cytokines (IL-31, IL-33, and inflammatory chemokines such as CCL17 and CCL22) were significantly reduced in the PA+AX group compared with the PA group. The expression of inflammatory genes (iNOS, COX-2, NF-kB and signaling molecules (p-IkBα, p50, p65, and p-STAT 3) was lower in the PA+AX group compared with the PA group. Conclusion: Astaxanthin may modulate the inflammatory response in a mouse model of atopic dermatitis and has an anti-inflammatory effect.

Effects and Efficacy of Natural Product on Infectious Diseases of pseudomonas aeruginosa (천연물 유래 물질이 감염성 질환에 미치는 영향과 효능)

  • Ji-Won Park
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2020.12a
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    • pp.3-13
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    • 2020
  • Pseudomonas aeruginosa is a ubiquitous gram-negative bacterium causing serious infections. The P. aeruginosa T3SS is a syringe-like apparatus on the bacterial surface, with 4 effector toxins: ExoS, ExoT, ExoY, and ExoU. Here, we investigated the effect of ExoS and ExoT of the T3SS of P. aeruginosa K strain (PAK). The type three secretion system (T3SS) is a major virulence system of Pseudomonas aeruginosa (P. aeruginosa). The effector protein Exotoxin S (ExoS) produced by P. aeruginosa is secreted into the host cells via the T3SS. For the purpose of screening the inhibitors with regard to ExoS secretion, we developed the sandwich-type enzyme-linked immunosorbent assay (ELISA) system. PAK clinical strains induce proinflammatory cytokine production through the T3SS, and this involves NF-κB activation in pneumonia mouse models. We tried to confirm the role of the NF-κB transcription factor in ExoS- and ExoT-induced pneumonia mouse models. pro-inflammatory cytokines induction in response to ExoS and ExoT infection relied on NF-κB activation. Our findings highlight the roles of natural poduct in inhibiting proinflammatory cytokine expression during ExoS and ExoT exposure in PAK infections, paving the way for a novel therapeutic approach for the treatment of pulmonary infections.

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NF-κB Activation and PPAR Transactivational Effects of a New Aliphatic Acid Amide from Pericarps of Zanthoxylum piperitum

  • Yang, Seo Young;Tai, Bui Huu;Song, Seok Bean;Li, Wei;Yan, Xi Tao;Sun, Ya Nan;Nguyen, Phuong Thao;Kim, Young Ho
    • Bulletin of the Korean Chemical Society
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    • v.35 no.8
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    • pp.2361-2366
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    • 2014
  • A new aliphatic acid amide, ZP-amide F (1), and eight known compounds, including bungeanumamide A (2), tumuramide C (3), ZP-amide A (4), ZP-amide B (5), ZP-amide D (6), hyperin (7), quercitrin (8), and (-)-sesamin (9), were isolated from pericarps of Zanthoxylum piperitum. The effects of these compounds on $TNF{\alpha}$-induced NF-${\kappa}B$ activation and transactivational activity of PPARs, including $PPAR{\alpha}$, $PPAR{\beta}({\delta})$ and $PPAR{\gamma}$ subtypes, were evaluated. Compounds 7 and 9 exhibited potent inhibitory effects on $TNF{\alpha}$-induced NF-${\kappa}B$ activation with $IC_{50}$ values of 5.50 and $8.10{\mu}M$, respectively. Aliphatic acid amide compounds 3, 4 and 6 displayed enhanced effects on PPAR transactivational activity with $EC_{50}$ values of 47.12, 19.13 and $12.02{\mu}M$, respectively. Among them, compound 4 demonstrated an increase in $PPAR{\alpha}$ transactivational activity, compound 3 showed a moderate increase on all PPAR subtypes, whereas compound 6 displayed weak PPAR transactivational activity.

Lactic Acid Bacteria Isolated from Human Breast Milk Improve Colitis Induced by 2,4,6-Trinitrobenzene Sulfonic Acid by Inhibiting NF-κB Signaling in Mice

  • Kyung-Joo Kim;Suhyun Kyung;Hui Jin;Minju Im;Jae-won Kim;Hyun Su Kim;Se-Eun Jang
    • Journal of Microbiology and Biotechnology
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    • v.33 no.8
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    • pp.1057-1065
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    • 2023
  • Inflammatory bowel disease (IBD), a chronic inflammatory disease, results from dysregulation of the immune responses. Some lactic acid bacteria (LAB), including Lactobacillus, alleviate IBD through immunomodulation. In this study, the anti-colitis effect of LAB isolated from human breast milk was investigated in a mouse model induced acute colitis with 2,4,6-trinitrobenzene sulfonic acid (TNBS). TNBS remarkably increased weight loss, colon shortening, and colonic mucosal proliferation, as well as the expression levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1β. Oral administration of LAB isolated from human breast milk resulted in a reduction in TNBS-induced colon shortening, as well as induced cyclooxygenase (COX)-2, nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB). In addition, LAB suppressed inflammatory cytokines such as TNF-α, IL-6, and IL-1β, and thus showed an effect of suppressing the level of inflammation induced by TNBS. Furthermore, LAB alleviated gut microbiota dysbiosis, and inhibited intestinal permeability by increasing the expression of intestinal tight junction protein including ZO-1. Collectively, these results suggest that LAB isolated from human breast milk can be used as a functional food for colitis treatment by regulating NF-κB signaling, gut microbiota and increasing expression of intestinal tight junction protein.

The Effect of Moutan Cortex on Pro-inflammatory Cytokines through NF-κB & MAPKs pathway in HMC-l (목단피의 NF-κB와 MAPKs 억제를 통한 Pro-inflammatory Cytokines 활성에 미치는 효과)

  • Park, Joo-Ho;Kim, Kyung-Jun
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.22 no.2
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    • pp.1-18
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    • 2009
  • Objective : Moutan Cortex (the root bark of Paeonia suffruticosa Andr.) is widely used in oriental medicine as a remedy for inflammation. However, as yet there is no clear explanation of how MC(Moutan Cortex) affects the production of inflammatory cytokine. This study was to determine the effects of Essence extracted MC on the mast cell-mediated inflammatory responses. Method : We observed the effect of MC on compound 48/80-induced histamine release of rat peritoneal mast cells and the effect of administering MC on PCA in rat. We measured the amount of inflammatory cytokine production induced by the phorbol myristate acetate (PMA) plus calcium ionophore(A23187) in the human mast cell line (HMC-1) incubated with various concentrations of MC. The TNF-$\alpha$ protein levels were analysised by Western blot. The TNF-$\alpha$, IL-6 and IL-8 secreted protein levels were measured by the ELISA assay. The TNF-$\alpha$, IL-6 and IL-8 mRNA levels were measured by the RT-PCR analysis. NF-$\kappa$B, phospho-I$\kappa$B and MAPKs were exmined by Western blot analysis. The NF-$\kappa$B promoter activity was examined by luciferase assay. Result : 1. Enzyme immunoassay indicated that MC suppressed histamine secretion of rat peritoneal mast cells. 2. In PCA dependent on IgE, MC had anti-allergic effect of the internal surface of rat skin. 3. Western blot indicated that MC decreased TNF-$\alpha$ protein levels. 4. ELISA indicated that MC decreased TNF-$\alpha$, IL-6 but MC had no significant effect on IL-8 in HMC-1 cells. 5. RT-PCR indicated that MC decreased TNF-$\alpha$, IL-8 but MC had no significant effect on IL-6 in HMC-l cells. 6. Western blot indicated that MC suppressed the induction of MAPKs, NF-$\kappa$B & phospho-I$\kappa$B activity in HMC-1 cells. 7. Luciferase assay indicated that MC suppressed the PMA plus A23187-induced NF-$\kappa$B promoting activityin HMC-1 cells. Conclusion : In this study, we have found that MC is an inhibitor of NF-$\kappa$B, MAPKs & cytokines on the mast cell-mediated inflammatory responses.

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A Splice Variant of the C2H2-Type Zinc Finger Protein, ZNF268s, Regulates NF-κB Activation by TNF-α

  • Chun, Jung Nyeo;Song, In Sung;Kang, Dong-Hoon;Song, Hye Jin;Kim, Hye In;Suh, Ja Won;Lee, Kong Ju;Kim, Jaesang;Won, Sang
    • Molecules and Cells
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    • v.26 no.2
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    • pp.175-180
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    • 2008
  • $I{\kappa}B$ kinase (IKK), the pivotal kinase in signal-dependent activation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$), is composed of multiple protein components, including IKK ${\alpha}/{\beta}/{\gamma}$ core subunits. To investigate the regulation of the IKK complex, we immunoaffinity purified the IKK complex, and by MALDI-TOF mass spectrometry identified a splice variant of zinc finger protein 268 (ZNF268) as a novel IKKinteracting protein. Both the full-length and the spliced form of the ZNF268 protein were detected in a variety of mammalian tissues and cell lines. The genes were cloned and expressed by in vitro transcription/translation. Several deletion derivatives, such as KRAB domain (KRAB) on its own, the KRAB/spacer/4-zinc fingers (zF4), and the spacer/4-zinc fingers (zS4), were ectopically expressed in mammalian cells and exhibited had different subcellular locations. The KRAB-containing mutants were restricted to the nucleus, while zS4 was localized in the cytosol. TNF-${\alpha}$-induced NF-${\kappa}B$ activation was examined using these mutants and only zS4 was found to stimulate activation. Collectively, the results indicate that a spliced form of ZNF268 lacking the KRAB domain is located in the cytosol, where it seems to play a role in TNF-${\alpha}$-induced NF-${\kappa}B$ activation by interacting with the IKK complex.

Vascular Smooth Muscle Cells Secrete CXCL10 in Response to Heat Shock Protein 90 (혈관평활근세포에서 HSP90에 의한 CXCL10 증가에 관여하는 인자에 대한 연구)

  • Rhim, Byung-Yong;Kim, Do-Hyung;Kim, Koan-Hoi
    • Journal of Life Science
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    • v.21 no.5
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    • pp.664-670
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    • 2011
  • Oxidative stress results in sustained release of heat shock protein 90 (HSP90) from vascular smooth muscle cells (VSMCs). We investigated whether extracellular HSP90 predisposed VSMCs to pro-inflammatory phenotype. Exposure of human aortic smooth muscle cells to HSP90 not only significantly enhanced CXCL10 secretion but also increased CXCL10 transcription. HSP90-mediated CXCL10 secretion was attenuated by OxPAPC, a TLR-2/4 inhibitor, and curcumin, a TLR-4 dimerization inhibitor. Inhibitors of diphenyleneiodium chloride and the Akt pathway also attenuated CXCL10 secretion in response to HSP90. The gene delivery of I${\kappa}$B using recombinant adenoviruses and treatment with resveratrol, which inhibit NF-${\kappa}$B activity, significantly attenuated HSP90-induced CXCL10 secretion from VSMCs. We propose that extracellular HSP90 contributes to an inflammatory reaction in the stressed vasculature by inducing CXCL10 expression of VSMCs, and that TLR-4, Akt, and NF-${\kappa}$B play active roles in the process.

Inductively coupled Plasma Reactive ion etching of Ge doped silica glass using $C_2F_6$ and $NF_3$ ($C_2F_6$$NF_3$ 유도결합플라즈마를 이용한 $SiO_2$:Ge 식각에관한 연구)

  • 이석룡;문종하;김원효;이병택
    • Proceedings of the Materials Research Society of Korea Conference
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    • 2003.11a
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    • pp.225-225
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    • 2003
  • 실리카글라스를 기초로 하는 PLC소자는 가격, 광 손실 성질과 광섬유와의 결합효율이 좋아 광통신에 응용되어지고 있으며 Ge 도핑된 실리카 글라스는 PLC소자의 코어물질로 널리 사용되고 있다. 소작제작을 위해서는 높은 식각률과 깨끗하고 적은 표면손상을 얻어야 하므로 유도결합플라즈마를 이용한 건식식각공정개발이 이루어 져야 한다. 본 연구에서는 Ge 도핑된 실리카글라스의 식각특성을 연구하기 위해 $C_2$F/6 와 NF$_3$가스를 사용하였고 ICP power, bias power, 압력, 플라즈마와 샘플간의 거리를 변화시키면서 식각속도, 표면거칠기, 메사수직도, 마스크선택도등 기본공정 조건을 연구하고 첨가가스(CH$_4$, $O_2$), 마스크 물질(Ni, Cr, PR) 도핑농도(0.3, 0.45, 0.7%)등을 변화시키면서 식각특성을 연구하였다. 그 결과 300nm/min, 정도의 식각속도를 가지고 수직한 메사각도(~89$^{\circ}$)와 미려한 표면(표면거 칠기 1.5nm 이하)를 갖는 결과를 얻었다.

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Single I/O System Using ENBD on Linux PC Clusters (리눅스 PC 클러스터에서 ENBD를 이용한 SIOS)

  • 김태규;김방현;김종현
    • Proceedings of the Korean Information Science Society Conference
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    • 2004.04a
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    • pp.4-6
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    • 2004
  • 클러스터 컴퓨터에서 접속된 모든 노드들의 디스크들을 통합 사용하기 위한 SIOS의 구현은 사용자 레벨과 파일 시스템 레벨, 그리고 디바이스 드라이버 레벨로 분류할 수 있다. 본 연구에서 제안하는 방법은 현재 공개되어 있는 소프트웨어 라이브러리만을 이용하여 리눅스 클러스터에서 SIOS를 구현하는 방법으로서, 확장 네트워크 블록 디바이스(ENBD: Enhanced Network Block Device)를 이용한 디바이스 드라이버 레벨의 하위 계층과 S/W RAID 및 NFS를 이용한 파일 시스템 레벨의 상위 계층으로 구성된다. 이 방법의 주요 장점은 현재 공개되어 있는 소프트웨어 라이브러리를 이용하기 때문에 구현이 용이하고 비용이 들지 않는다는 점이다. 그리고 하위 계층으로서 디바이스 드라이버 레벨의 ENBD를 이용하기 때문에 파일 시스템을 변경하지 않기 때문에 이전의 응용 프로그램에 대한 호환성이 높다. 또한, 상위 계층에서는 파일 시스템 레벨의 S/W RAID와 NFS를 이용함에 따라 디스크 배열 방식의 조정이 비교적 자유롭다. 또 다른 장점은 하위 계층과 상위 계층이 서로 독립적이기 때문에, 클러스터의 사용 목적에 따라 각 계층을 다양한 방법으로 변경할 수 있다는 것이다. Bonnie 벤치마크를 이용한 성능 측정 결과에 따르면, ENBD를 이용하여 RAID-5로 구성한 경우에 오버헤드가 높은 NFS를 사용했음에도 불구하고 비용이 많이 드는 다른 방법과 대등한 성능을 보였으며, 부분적으로는 더 높은 성능과 확장성을 가지는 것으로 나타났다.

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