• Title/Summary/Keyword: NF$\kappa$B

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Ginsenosides Inhibit HMGB1-induced Inflammatory Responses in HUVECs and in Murine Polymicrobial Sepsis

  • Lee, Wonhwa;Ku, Sae-Kwang;Jeong, Tae Cheon;Lee, Sangkyu;Bae, Jong-Sup
    • Bulletin of the Korean Chemical Society
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    • v.35 no.10
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    • pp.2955-2962
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    • 2014
  • Asian ginseng is used as a treatment for cardiovascular diseases, ischemia, and cancers. High mobility group box 1 (HMGB1) protein acts as a late mediator of severe vascular inflammatory conditions. However, the effect of ginsenosides from Asian ginseng on HMGB1-induced inflammatory responses has not been studied. We addressed this question by monitoring the effects of ginsenoside treatment on lipopolysaccharide (LPS) and cecal ligation and puncture (CLP)-mediated release of HMGB1, and HMGB1-mediated regulation of proinflammatory responses. Ginsenoside treatment suppressed LPS-mediated release of HMGB1 and HMGB1-mediated cytoskeletal rearrangements. Ginsenosides also inhibited HMGB1-mediated inflammatory responses. In addition, ginsenosides inhibited the production of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and activation of protein kinase B (Akt), nuclear factor-${\kappa}B$ (NF-${\kappa}B$), and extracellular-regulated kinases (ERK) 1/2 by HMGB1. Ginsenosides also decreased CLP-induced release of HMGB1, production of interleukin (IL) $1{\beta}/6$, and mortality. These results suggested that ginsenosides may be potential therapeutic agents for treatment of vascular inflammatory diseases through inhibition of the HMGB1 signaling pathway.

Anti-Inflammatory Potential of Probiotic Strain Weissella cibaria JW15 Isolated from Kimchi through Regulation of NF-κB and MAPKs Pathways in LPS-Induced RAW 264.7 Cells

  • Yu, Hyung-Seok;Lee, Na-Kyoung;Choi, Ae-Jin;Choe, Jeong-Sook;Bae, Chun Ho;Paik, Hyun-Dong
    • Journal of Microbiology and Biotechnology
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    • v.29 no.7
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    • pp.1022-1032
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    • 2019
  • Probiotics are known to provide the host with immune-modulatory effects and are therefore of remarkable interest for therapeutic and prophylactic applications against various disorders, including inflammatory diseases. Weissella cibaria JW15 (JW15) has been reported to possess probiotic and antioxidant properties. However, the effect of JW15 on inflammatory responses has not yet been reported. Therefore, the objective of the current study was to evaluate the anti-inflammatory potential of JW15 against lipopolysaccharide (LPS) stimulation. The production of pro-inflammatory factors and the cellular signaling pathways following treatment with heat-killed JW15 was examined in LPS-induced RAW 264.7 cells. Treatment with heat-killed JW15 decreased nitric oxide and prostaglandin $E_2$ production via down-regulation of the inducible nitric oxide synthase and cyclooxygenase-2. In addition, treatment with heat-killed JW15 suppressed the expression of pro-inflammatory cytokines, interleukin $(IL)-1{\beta}$, IL-6, and tumor necrosis factor-${\alpha}$. The anti-inflammatory properties of treating with heat-killed JW15 were associated with mitogen-activated protein kinase signaling pathway-mediated suppression of nuclear factor-${\kappa}B$. These results indicated that JW15 possesses anti-inflammatory potential and provide a molecular basis regarding the development of functional probiotic products.

The anti-inflammatory effect of Taraxacum coreanum on lipopolysaccharide induced inflammatory response on RAW 264.7 cells (LPS로 유도한 RAW 264.7 세포의 염증반응에서 흰민들레의 항염증 효과)

  • Kim, Min-Jun;Bae, Gi-Sang;Choi, Sun Bok;Jo, Il-Joo;Kim, Dong-Goo;Shin, Joon-Yeon;Lee, Sung-Kon;Kim, Myoung-Jin;Park, Sung-Joo;Song, Ho-Joon
    • The Korea Journal of Herbology
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    • v.29 no.6
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    • pp.21-26
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    • 2014
  • Objectives : Taraxacum coreanum (TC) have been used as a traditional medicine to treat inflammatory diseases and anti-oxidant effect in Korea. However, the anti-inflammatory effect of TC water extract on lipopolysaccharide (LPS)-induced inflammation is not well-known. Therefore, this study was performed to identify the anti-inflammatory effect of TC on LPS induced inflammatory. Methods : RAW 264.7 cells were treated with 500 ng/mL of LPS. Water extracts of TC (0.1, 0.25, 0.5 mg/ml) was treated 1 h prior to LPS. Cell viability was measured by MTT assay. Levels of nitric oxide (NO) were measured with Griess reagent and pro-inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (real-time PCR). We also examined molecular mechanisms such as mitogen-activated protein kinases (MAPKs) and nuclear factor-B ($NF-{\kappa}B$) activation by western blot. Results : Water Extract from TC itself did not have any cytotoxic effect in RAW 264.7 cells. TC treatment inhibited the production of NO production, and pro-inflamamtory cytokines such as interleukin (IL)-6 and $IL-1{\beta}$ on protein and mRNA levels. In addition, TC treatment inhibited the LPS-induced activation of MAPKs such as extracellular signal-regulated kinase1/2 (ERK1/2), p38 kinases (p38), c-Jun $NH_2$-terminal kinase (JNK) and $NF-{\kappa}B$. Conclusions : In summary, our result suggest that treatment of TC could reduce the LPS-induced inflammation. Thereby, TC could be used as a protective agent against inflammation. Also, this study could give a clinical basis that TC could be a drug or agent to prevent inflammation.

Folic acid supplementation regulates key immunity-associated genes and pathways during the periparturient period in dairy cows

  • Khan, Muhammad Zahoor;Zhang, Zhichao;Liu, Lei;Wang, Di;Mi, Siyuan;Liu, Xueqin;Liu, Gang;Guo, Gang;Li, Xizhi;Wang, Yachun;Yu, Ying
    • Asian-Australasian Journal of Animal Sciences
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    • v.33 no.9
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    • pp.1507-1519
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    • 2020
  • Objective: The current research was aimed to profile the transcriptomic picture of the peripheral blood lymphocytes (PBLs) associated with immunity in Chinese Holsteins supplemented orally with coated folic acid during the periparturient period. Methods: The total of 123 perinatal cows were selected for this study and divided into three groups; group A (n = 41, 240 mg/500 kg cow/d), group B (n = 40, 120 mg/500 kg cow/d) and group C (n = 42, 0 mg/cow/d) based on the quantity of folic acid fed. Three samples of PBLs were selected from each folic acid treated group (high, low, and control) and RNA sequencing method was carried out for transcriptomic analysis. Results: The analysis revealed that a higher number of genes and pathways were regulated in response to high and low folic acid supplementation compared to the controls. We reported the novel pathways tumor necrosis factor (TNF) signaling, antigen processing and presentation, Staphylococcus aureus infection and nuclear factor (NF)-kappa B signaling pathways) and the key genes (e.g. C-X-C motif chemokine ligand 10, TNF receptor superfamily member 1A, cluster difference 4, major histocompatibility complex, class II, DQ beta, NF-kappa-B inhibitor alpha, and TNF superfamily 13) having great importance in immunity and anti-inflammation in the periparturient cows in response to coated folic acid treatment. Conclusion: Collectively, our study profiled first-time transcriptomic analysis of bovine lymphocytes and compared the involved cytokines, genes, and pathways between high vs control and low vs control. Our data suggest that the low folic acid supplementation (120 mg/500 kg) could be a good choice to boost appropriate immunity and anti-inflammation as well as might being applied to the health improvement of perinatal dairy cows.

Rutin alleviated lipopolysaccharide-induced damage in goat rumen epithelial cells

  • Jinshun Zhan;Zhiyong Gu;Haibo Wang;Yuhang Liu;Yanping Wu;Junhong Huo
    • Animal Bioscience
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    • v.37 no.2
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    • pp.303-314
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    • 2024
  • Objective: Rutin, also called vitamin P, is a flavonoids from plants. Previous studies have indicated that rutin can alleviate the injury of tissues and cells by inhibiting oxidative stress and ameliorating inflammation. There is no report on the protective effects of rutin on goat rumen epithelial cells (GRECs) at present. Hence, we investigated whether rutin can alleviate lipopolysaccharide (LPS)-induced damage in GRECs. Methods: GRECs were cultured in basal medium or basal medium containing 1 ㎍/mL LPS, or 1 ㎍/mL LPS and 20 ㎍/mL rutin. Six replicates were performed for each group. After 3-h culture, the GRECs were harvested to detect the relevant parameters. Results: Rutin significantly enhanced the cell activity (p<0.05) and transepithelial electrical resistance (TEER) (p<0.01) and significantly reduced the apoptosis rate (p<0.05) of LPS-induced GRECs. Rutin significantly increased superoxide dismutase, glutathione peroxidase, and catalase activity (p<0.01) and significantly decreased lactate dehydrogenase activity and reactive oxygen species and malondialdehyde (MDA) levels in LPS-induced GRECs (p<0.01). The mRNA and protein levels of interleukin 6 (IL-6), IL-1β, and C-X-C motif chemokine ligand 8 (CXCL8) and the mRNA level of tumor necrosis factor-α (TNF-α) and chemokine C-C motif ligand 5 (CCL5) were significantly increased in LPS-induced GRECs (p<0.05 or p<0.01), while rutin supplementation significantly decreased the mRNA and protein levels of IL-6, TNF-α, and CXCL8 in LPS-induced GRECs (p<0.05 or p<0.01). The mRNA level of toll-like receptor 2 (TLR2), and the mRNA and protein levels of TLR4 and nuclear factor κB (NF-κB) was significantly improved in LPS-induced GRECs (p<0.05 or p<0.01), whereas rutin supplementation could significantly reduce the mRNA and protein levels of TLR4 (p<0.05 or p<0.01). In addition, rutin had a tendency of decreasing the protein levels of CXCL6, NF-κB, and inhibitor of nuclear factor kappa-B alpha (0.05

The Role of Receptor Activator of NF-κ Ligand in Smooth Muscle Cell Proliferation (Smooth muscle cell 증식에 있어 NF-κ ligand의 receptor activator의 역할)

  • Kim, Hyun-Ju
    • Journal of Life Science
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    • v.16 no.6
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    • pp.1066-1070
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    • 2006
  • Smooth muscle cell (SMC) proliferation is important in the pathogenesis of vascular proliferative disorders. Understanding of the molecular mechanism underlying SMC growth after arterial injury would have therapeutic implications. Here we report that receptor activator of $NF-{\kappa}B$ ligand (RANKL), a member of tumor necrosis factor (TNF) family, promotes the proliferation of SMC, leading to decreased expression of p21 and enhancement of SMC growth. ERK and p38 phosphorylation was enhanced after RANKL treatment in SMC. Inhibition of ERK/p38 MAPK activity by PD98059/SB203580 completely abolished RANKL-induced proliferation of SMC, indicating ERK and p38 MAPK are essential for RANKL-induced SMC proliferation. Taken together, our findings demonstrate that RANK-RANKL-ERK/p38 pathway is important for proliferation of SMC and that these molecules may be the new therapeutic targets for the prevention of vascular diseases.

Anti-inflammatory Effect of Geumeunwha-san Water Extract on LPS-induced Raw 264.7 Cells (금은화산(金銀花散)의 LPS로 유도된 Raw 264.7 세포에서의 항염증 효과)

  • Kim, Yeon-Soo;Kim, Su-Jin;Jee, Seon-Young;Hwangbo, Min
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.34 no.3
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    • pp.1-12
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    • 2021
  • Objectives : The purpose of this study is to investigate the anti-inflammatory effect of Geumeunwha-san(GEHS) water extract in vitro. Methods : To evaluate the anti-inflammatory effect of GEHS, Raw 264.7 cells were pretreated with 10-300㎍/㎖ of GEHS for 1hr, and then exposed to 1㎍/㎖ of LPS. MTT assay was used to detect the cell viability. Productions of pro-inflammatory cytokines and NO were measured in culture media. By using immunoblot analysis, protein levels of iNOS and NF-𝜅B were determined. Results : In vitro study, cell viability assay on GEHS treatment of 10-300㎍/㎖ has no cytotoxicity in Raw 264.7 cells. Pretreated 100, 300㎍/㎖ of GEHS had significantly inhibited LPS-induced NO production. And also pretreatment of 100, 300㎍/㎖ GEHS had significantly decreased production of interleukin-6, -1𝛽 and tumor necrosis factor-𝛼 in LPS-activated Raw 264.7 cells. In addition, GEHS reduced LPS-mediated iNOS expression. Moreover I-𝜅B𝛼 expression was significantly induced by GEHS and NF-𝜅B expression was reduced by GEHS. Conclusions : These results suggest the clinical basis of GEHS for the treatment of inflammatory diseases.

Pear pomace alleviated atopic dermatitis in NC/Nga mice and inhibited LPS-induced inflammation in RAW 264.7 macrophages

  • You, Mikyoung;Wang, Ziyun;Kim, Hwa-Jin;Lee, Young-Hyun;Kim, Hyeon-A
    • Nutrition Research and Practice
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    • v.16 no.5
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    • pp.577-588
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    • 2022
  • BACKGROUND/OBJECTIVES: Poorly regulated inflammation is believed to be the most predominant factor that can result in a wide scope of diseases including atopic dermatitis (AD). Despite many studies on the effect of pear pomace in obesity-related disorders including dysregulated gut microbiota, the protective effect of pear pomace in AD is still unknown. This study aimed to evaluate the effect of pear pomace ethanol extract (PPE) on AD by inhibiting inflammation. MATERIALS/METHODS: In the in vivo experiment, 2, 4-dinitrochlorobenzene (DNCB) was applied to NC/Nga mice to induce AD-like skin lesions. After the induction, PPE was administered daily by oral gavage for 4 weeks. The clinical severity score, serum IgE levels, spleen weight, histological changes in dorsal skin, and inflammation-related proteins were measured. In the cell study, RAW 264.7 cells were pretreated with PPE before stimulation with lipopolysaccharide (LPS). Nitrite oxide (NO) production and nuclear factor kappa B (NF-𝛋B) protein expression were detected. RESULTS: Compared to the AD control (AD-C) group, IgE levels were dramatically decreased via PPE treatment. PPE significantly reduced scratching behavior, improved skin symptoms, and decreased ear thickness compared to the AD-C group. In addition, PPE inhibited the DNCB-induced expression of inducible nitrite oxide synthase (iNOS), the receptor for advanced glycation end products, extracellular signal-regulated kinase (ERK) 1/2, and NF-𝛋B. PPE inhibited the LPS-induced overproduction of NO and the enhanced expression of iNOS and cyclooxygenase-2. Moreover, the phosphorylation of ERK1/2 and NF-𝛋B in RAW 264.7 cells was suppressed by PPE. CONCLUSIONS: These results suggest that PPE could be explored as a therapeutic agent to prevent AD.

Lactobacillus plantarum C29 Alleviates TNBS-Induced Memory Impairment in Mice

  • Lee, Hae-Ji;Jeong, Jin-Ju;Han, Myung Joo;Kim, Dong-Hyun
    • Journal of Microbiology and Biotechnology
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    • v.28 no.1
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    • pp.175-179
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    • 2018
  • In a preliminary study, Lactobacillus plantarum C29 was found to suppress 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in mice. Therefore, to understand whether an anti-colitic probiotic C29 could attenuate memory impairment, we examined the effects of C29 on TNBS-induced memory impairment in mice. Orally administered Lactobacillus plantarum C29 attenuated TNBS-induced memory impairment in mice in the Y-maze, noble object, and passive avoidance task tests. C29 treatment increased TNBS-suppressed hippocampal brain-derived neurotrophic factor expression and inhibited TNBS-induced hippocampal NF-${\kappa}B$ activation and blood LPS levels. Moreover, C29 restored the TNBS-disturbed gut microbiota composition. These findings suggest that C29 can alleviate memory impairment presumably by restoring the gut microbiota composition.