• Title/Summary/Keyword: NF-$\kappaB$

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Heat-Killed Lactobacillus plantarum KCTC 13314BP Enhances Phagocytic Activity and Immunomodulatory Effects via Activation of MAPK and STAT3 Pathways

  • Jeong, Minju;Kim, Jae Hwan;Yang, Hee;Kang, Shin Dal;Song, Seongbong;Lee, Deukbuhm;Lee, Ji Su;Park, Jung Han Yoon;Byun, Sanguine;Lee, Ki Won
    • Journal of Microbiology and Biotechnology
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    • v.29 no.8
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    • pp.1248-1254
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    • 2019
  • Identification of novel probiotic strains is of great interest in the field of functional foods. Specific strains of heat-killed bacteria have been reported to exert immunomodulatory effects. Herein, we investigated the immune-stimulatory function of heat-killed Lactobacillus plantarum KCTC 13314BP (LBP). Treatment with LBP significantly increased the production of $TNF-{\alpha}$ and IL-6 by macrophages. More importantly, LBP was able to enhance the phagocytic activity of macrophages against bacterial particles. Activation of p38, JNK, ERK, $NF-{\kappa}B$, and STAT3 was involved in the immunomodulatory function of LBP. LBP treatment significantly increased production of $TNF-{\alpha}$ by bone marrow-derived macrophages and splenocytes, further confirming the immunostimulatory effect of LBP in primary immune cells. Interestingly, the immunomodulatory effects of LBP were much stronger than those of Lactobacillus rhamnosus GG, a well-known probiotic strain. These results indicate that LBP can be a promising immune-enhancing functional food agent.

Dose-Dependent Inhibition of Melanoma Differentiation-Associated Gene 5-Mediated Activation of Type I Interferon Responses by Methyltransferase of Hepatitis E Virus

  • Myoung, Jinjong;Min, Kang Sang
    • Journal of Microbiology and Biotechnology
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    • v.29 no.7
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    • pp.1137-1143
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    • 2019
  • Hepatitis E virus (HEV) accounts for 20 million infections in humans worldwide. In most cases, the infections are self-limiting while HEV genotype 1 infection cases may lead to lethal infections in pregnant women (~ 20% fatality). The lack of small animal models has hampered detailed analysis of virus-host interactions and HEV-induced pathology. Here, by employing a recently developed culture-adapted HEV, we demonstrated that methyltransferase, a non-structural protein, strongly inhibits melanoma differentiation-associated gene 5 (MDA5)-mediated activation of type I interferon responses. Compared to uninfected controls, HEV-infected cells display significantly lower levels of $IFN-{\beta}$ promoter activation when assessed by luciferase assay and RT-PCR. HEV genome-wide screening showed that HEV-encoded methyltransferase (MeT) strongly inhibits MDA5-mediated transcriptional activation of $IFN-{\beta}$ and $NF-{\kappa}B$ in a dose-responsive manner whether or not it is expressed in the presence/absence of a tag fused to it. Taken together, current studies clearly demonstrated that HEV MeT is a novel antagonist of MDA5-mediated induction of $IFN-{\beta}$ signaling.

Expression of ssrA in non-pathogen-induced adaptation in the oral cavity through signal exchange with oral pathogens

  • Kim, Sung-Ryoul;Kwak, Jae-Woo;Lee, Sung-Ka;Jung, Seung-Gon;Han, Man-Seung;Kim, Bang-Sin;Kook, Min-Suk;Oh, Hee-Kyun;Park, Hong-Ju
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.38 no.1
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    • pp.14-19
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    • 2012
  • Introduction: This study was conducted to evaluate ssrA expression resulting from adaptation of Escherichia coli (E. coli) to oral pathogens through signal exchange. Materials and Methods: Human cell lines Hep2 and HT29, wild-type E. coli (WT K-12), ssrA knock-out E. coli (${\Delta}K$-12), and Scleropages aureus (S. aureus) were used. A single culture consisting of Hep2, HT29, WT K-12, and ${\Delta}K$-12, and mixed cultures consisting of Hep2 and WT K-12, Hep2 and ${\Delta}K$-12, WT K-12 and S. aureus, ${\Delta}K$-12 and S. aureus, and Hep2, WT K-12, and S. aureus were prepared. For HT29, a mixed culture was prepared with WT K-12 and with WT K-12 and S. aureus. Total RNA was extracted from each culture with the resulting expression of ssrA, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-${\kappa}B$), and p53 was evaluated by Reverse transcription polymerase chain reaction (RT-PCR). Results: The expression of ssrA in a single culture of WT K-12 was lower than that observed in the mixed culture of WT K-12 with S. aureus. Greater ssrA expression was observed in the mixed culture of WT K-12 with Hep2 than in the single culture of WT K-12. The expression of NF-${\kappa}B$ was higher in the mixed culture of Hep2 with ${\Delta}K$-12 than that in the mixed culture of Hep2 with WT K-12, and was lowest in the single culture of Hep2. The expression of ssrA was higher in the mixed culture of WT K-12 with Hep2 and S. aureus than in the mixed culture of WT K-12 with Hep2. Conclusion: These results suggest that ssrA plays an important role in the mechanism of E. coli adaptation to a new environment.

The Effects of Several Halophytes on Insulin Resistance in Otsuka Long-evans Tokushima Fatty Rats (OLETF 쥐에서 칠면초와 세발나물의 인슐린 저항성 개선 효과)

  • Cho, Jeong-Yong;Huang, Zhangjun;Park, Sun-Young;Park, Kyung-Hee;Pai, Tong-Kun;Kim, So-Young;Kim, Haeng-Ran;Ham, Kyung-Sik
    • Korean Journal of Food Science and Technology
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    • v.46 no.1
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    • pp.100-107
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    • 2014
  • We evaluated preventive effects of Suaeda japonica (SJ) and Spergularia marina Griseb (SMG) on the insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. The 10-week old OLETF rats were fed diets containing 3% (w/w) SJ and SMG for 18 weeks. Fasting blood glucose levels in SJ and SMG groups, measured using the oral glucose tolerance test, were lower than that of the control rats. The SMG group showed significantly lower levels of insulin, glycated hemoglobin, triglyceride, and total cholesterol than the control group. In addition, these levels were relatively lower in the SJ group than those in the control rats. The SJ and SMG groups had relatively lower protein levels of nuclear factor-kappa B (NF-${\kappa}B$) p65 in adipose tissue and serine phosphorylated insulin receptor substrate 1 (IRS-1) in skeletal muscle than the control group. These results suggest that SJ and SMG prevent insulin resistance and SMG in particular reduces blood triglyceride and total cholesterol levels.

Anti-inflammatory Effect of Sargassum coreanum Ethanolic Extract through Suppression of NF-κB Pathway in LPS Induced RAW264.7 Cells in Mice (LPS로 유도된 RAW 264.7 cell로부터 NF-κB 조절 억제와 마우스 모델을 통한 큰잎모자반 에탄올 추출물의 항염증 효과)

  • Kang, Bo-Kyeong;Kim, Koth-Bong-Woo-Ri;Kim, Min-Ji;Bark, Si-Woo;Pak, Won-Min;Ahn, Na-Kyung;Choi, Yeon-Uk;Bae, Nan-Young;Park, Ji-Hye;Ahn, Dong-Hyun
    • Microbiology and Biotechnology Letters
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    • v.43 no.2
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    • pp.112-119
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    • 2015
  • The anti-inflammatory effect of Sargassum coreanum ethanolic extract (SCEE) was investigated using lipopolysaccharide (LPS)-induced inflammatory responses in this study. It was shown that there was no cytotoxicity in the viability of macrophages treated with SCEE when compared to the control. The production of NO was considerably suppressed by SCEE, approximately up to 50% at 100 μg/ml. This significantly decreased levels of IL-6, TNF-α, and IL-1β. In addition, the expression of iNOS, COX-2, NF-κB was suppressed by SCEE treatment. In in vivo testing, the croton oil-induced mouse ear edema was attenuated by SCEE and there were no mortalities in mice administered with 5000 mg/kg body weight of SCEE over a 2 week observation period. From these results, SCEE inhibits the release of LPS-induced pro-inflammatory cytokines and mediators, suggesting that SCEE could be a potential agent for anti-inflammatory therapies.

Anti-inflammatory Activity of Extracts of Hovenia dulcis on Lipopolysaccharides-stimulated RAW264.7 Cells (LPS로 유도된 RAW264.7 대식세포에 대한 헛개나무(Hovenia dulcis) 추출물의 항염증 효과)

  • Woo, Hyun Sim;Lee, Sun Min;Heo, Jeong Doo;Lee, Min-Sung;Kim, Yeong-Su;Kim, Dae Wook
    • Korean Journal of Plant Resources
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    • v.31 no.5
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    • pp.466-477
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    • 2018
  • In this study, the anti-inflammatory activities of the extracts of different parts of Hovenia dulcis such as leaves, stems, and roots were investigated. Among them, the roots extract (RE) showed the most potent suppressive effect against pro-inflammatory mediators in LPS-stimulated mouse macrophage cells. RE induced dose-dependent reduction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and concomitantly reduced the production of NO and $PGE_2$. Additionally, pre-treatment with RE significantly suppressed the production of inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), interleukin $(IL)-1{\beta}$, and IL-6, as well as mRNA levels. Moreover, phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear translocation of nuclear factor-kappa B (NF-kB) were also strongly attenuated by RE in RAW264.7 cell. Furthermore, RE induced HO-1 expression through nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and increase HO-1 activity in RAW264.7 macrophages. Therefore, these results indicate that RE strongly inhibits LPS-induced inflammatory responses by blocking NF-kB activation, inhibiting MAPKs phosphorylation, and enhancing HO-1 expression in macrophages, suggesting that RE of H. dulicis and a major component, 27-O-protocatechuoylbetulinic acid could be applied as a valuable natural anti-inflammatory material.

Effects of Gene expression by Coptidis chinesis FRANCH. in a Hypoxic Model of Cultured Rat Cortical Cells (배양한 흰쥐 대뇌세포의 저산소증 모델에서 황련(黃連)이 유전자 표현에 미치는 영향)

  • Hwang, Joo-Won;Kim, Kyung-Hun;Shin, Gil-Cho;Moon, Il-Soo
    • The Journal of Internal Korean Medicine
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    • v.32 no.2
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    • pp.301-321
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    • 2011
  • Objectives : The purpose of this investigation was to evaluate the effects of Coptidis chinesis FRANCH. on the alteration of gene expression in a hypoxic model using cultured rat cortical cells. Methods : E18 rat cortical cells were grown in neurobasal medium containing B27 supplement. On 12 DIV, water extract from Coptidis chinesis FRANCH. was added ($20{\mu}g/ml$) to the culture media 4 hrs. On 14 DIV, cells were given hypoxic insult (2% $O_2$/5% $CO_2$, $37^{\circ}C$, 3 hrs), returned to normoxia and cultured for another 24 hrs. Total RNA was extracted from Coptidis chinesis FRANCH. treated and untreated cultures and alterations in the gene expression were analysed by microarray using rat 5K-TwinChips. Results : Effects on some of the genes whose functions were implicated in neural viability were as follows: the expression of apoptosis-related genes such as Clu (Global M = 1.3), of presynaptic inhibition's genes such as Penk-rs (Global M = 1.97), and of innate immuniti's such as Crp (Global M = 1.95), Defensin (Global M = 2.14), and Dnase1l3 (Global M = 1.57) increased. The expression of neurotrophic genes such as S100b (Global M = 1.42), and $NF{\kappa}B$ (Global M = 2.04) increased. Conclusions : Analysing the genes expressed on microarray, shows Coptidis chinesis FRANCH.protects cells by increasing viability and neural nutrition.

Detection and Characterization of PCR-SSCP Markers of the Bovine Lactoferrin Gene for Clinical Mastitis

  • Zhou, Lei;Yang, Yuan-Yuan;Li, Zhong-Hao;Kong, Li-Juan;Xing, Guan-Dong;Di, He-Shuang;Wang, Gen-Lin
    • Asian-Australasian Journal of Animal Sciences
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    • v.19 no.10
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    • pp.1399-1403
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    • 2006
  • A total of 80 cows, including 40 top mastitis resistant and 40 top mastitis susceptible animals as Group I and Group II, were selected from a population of 520 cows based on clinical mastitis occurrence. PCR-SSCP analysis on four fragments within the 5'region and two fragments of Exons 4,15 of bovine lactoferrin (bLF) revealed that four fragments-P1,P4,E4,E15-had polymorphisms which totally included six base mutations, and only two of them had significant differences in allele frequencies between resistant and susceptible groups, P1 (53.7% vs. 70.0%, p<0.05) and P4 (55.0% vs. 68.8%, p<0.05). Further study on these two promising markers combined with the milk performance traits of cows demonstrated that their selection would result in higher fat percentage (p<0.05), lower Somatic Cell Score (SCS) (p<0.05) and Clinical Mastitis Residuals (CMR) (p<0.01) indicating higher mastitis resistance and lower milk yield (p<0.05). The putative transcription factor binding sites in the 5'region were also studied by using MatInspector 7.2.2 software, and two signal pathways regulating the expression of bLF including the NF-${\kappa}B$ pathway and nuclear hormone receptor pathway were predicted.

Anti-Inflammatory Effects of Streamed Platycodon grandiflorum against UVB Radiation-Induced Oxidative Stress in Human Primary Dermal Fibroblast

  • Lee, Ji Yeon;Park, Jeong-Yong;Lee, Dae Young;Kim, Hyung Don;Kim, Geum-Soog;Lee, Seung Eun;Seo, Kyung Hye
    • The Korean Journal of Food And Nutrition
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    • v.31 no.4
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    • pp.495-501
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    • 2018
  • Ultraviolet B (UVB) exposure is a risk factor for skin damage resulting in oxidative stress, inflammation, and cell death. The purpose of this study was to investigate the physicochemical properties of Platycodon grandiflorum (PG) to improve its biological activities using a three-step steaming process. We investigated the protective effects of PG and steamed PG extracts on human dermal fibroblasts (HDFs) against UVB radiation-induced oxidative stress and inflammation as well as the underlying mechanisms. The antioxidant potential of the PG extracts was evaluated by measuring the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) scavenging activity. ABTS and DPPH were shown by the 0, 30, and 70% ethanol extracts of 2S-PG and 3S-PG ($IC_{50}$, 28~45 and $27{\sim}30{\mu}g/mL$, respectively). Treatment of UVB-irradiated cells with steamed PG ($25{\sim}400{\mu}g/mL$) did not affect their viability. The streamed PG extract suppressed UVB-induced generation of reactive oxygen species (ROS). In addition, streamed PG extract reduced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein expression in UVB-irradiated HDF, regulating nuclear factor $(NF)-{\kappa}B$ expression. These findings suggest that steamed PG extract may be potentially effective against inflammation associated with UVB-induced oxidation stress.

The Protective Effect of Chlorophyll a Against Oxidative Stress and Inflammatory Processes in LPS-stimulated Macrophages

  • Park, Ji-Young;Park, Chung-Mu;Kim, Jin-Ju;Noh, Kyung-Hee;Cho, Chung-Won;Song, Young-Sun
    • Food Science and Biotechnology
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    • v.16 no.2
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    • pp.205-211
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    • 2007
  • This study was designed to investigate the suppressive effect of chlorophyll a on nitric oxide (NO) production and intracellular oxidative stress. In addition, chlorophyll a regulation of nuclear factor (NF) ${\kappa}B$ activation and inducible NO synthase (iNOS) expression were explored as potential mechanisms of NO suppression in a lipopolysaccharide (LPS)-stimulated macrophage cell line. RAW 264.7 murine macrophages were preincubated with various concentrations ($0-10\;{\mu}g/ mL$) of chlorophyll a and stimulated with LPS to induce oxidative stress and inflammatory response. Treatment with chlorophyll a reduced the accumulation of thiobarbituric acid-reactive substances (TBARS), enhancing glutathione level and the activities of antioxidative enzymes including superoxide dismutase, catalase, glutathione peroxidase (GSH-px), and glutathione reductase in LPS-stimulated macrophages compared to LPS-only treated cells. NO production was significantly suppressed in a dose-dependent manner (p<0.05) with an $IC_{50}$ of $12.8\;{\mu}g/mL$. Treatment with chlorophyll a suppressed the levels of iNOS protein and its mRNA expression. The specific DNA binding activities of NFkB on nuclear extracts from chlorophyll a treated cells were significantly suppressed in a dose-dependent manner with an $IC_{50}$ of $10.7\;{\mu}g/mL$. Chlorophyll a ameliorates NO production and iNOS expression through the down-regulation of NFkB activity, which may be mediated by attenuated oxidative stress in RAW 264.7 macrophages.