• Title/Summary/Keyword: TNF signaling

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Salviae Radix Suppresses Mast Cell-mediated Allergic Response: Inhibition of Src-family Kinase (단삼추출물의 Src-family Kinase 억제에 의한 항앨러지 효과)

  • Kim, Young-Mi
    • YAKHAK HOEJI
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    • v.52 no.5
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    • pp.370-375
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    • 2008
  • In this study, the anti-allergic activity and mechanim of Salviae radix (SR) were investigated. The ethanol extract of SR showed significant inhibitory effect on degranulation from antigen-stimulated mast cells and it also inhibited the expression and secretion of TNF-${\alpha}$ and IL-4 in antigen-stimulated RBL-2H3 cells. In the mast cell-mediated local animal allergy model, it suppressed the passive cutaneous anaphylaxis in a dose-dependent manner. As its mechanism of action, SR inhibited the activating phosphorylation of Syk, a downstream signaling molecule of Src-family kinase, for the activation of mast cells. The results of the study indicate that the anti-allergic activity of SR is mediated by the inhibition of Src-family kinase in mast cells.

Lipoteichoic Acid Isolated from Staphylococcus aureus Induced THP-1 Cell Apoptosis through an Autocrine Mechanism of Cytokines and SOCS-1-Mediated Bcl2 Inhibition

  • Jeon, Boram;Kim, Hangeun;Chung, Dae Kyun
    • Microbiology and Biotechnology Letters
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    • v.50 no.2
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    • pp.293-300
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    • 2022
  • Lipoteichoic acid (LTA) regulates the immune system, including inflammatory responses, through TLR2-mediated signaling pathways. LTA isolated from Staphylococcus aureus (aLTA) has been shown to induce apoptosis, but the detailed mechanism has not been identified. We found that aLTA induced apoptosis through an autocrine mechanism in the human monocyte-like cell line, THP-1. We observed that the expression level of the anti-apoptosis protein, Bcl2, was suppressed in LTA-treated THP-1 cells. In addition, the cytokines, TNF-α and IFN-γ, which have been shown to induce apoptosis in some cell lines, were involved in THP-1 cell death via the modulation of Bcl2. The suppression of Bcl2 by aLTA was recovered when the negative regulator, SOCS-1, was knocked down. Taken together, these results showed that aLTA induced apoptosis in THP-1 cells through an autocrine mechanism of cytokines and SOCS-1-mediated Bcl2 inhibition.

Herbal Extracts as a NF-kappaB Inhibitor (NF-kappaB 프로모터 활성을 억제하는 식물추출물)

  • Park, Deok-Hoon;Lee, Jong-Sung;Jung, Eun-Sun;Hyun, Chang-Gu;Lee, Ji-Young;Hur, Sung-Ran;Koh, Jae-Sook;Lee, Hee-Kyung;Baek, Ji-Hwoon;Yoo, Byung-Sam;Moon, Ji-Young;Kim, Ju-Ho
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.32 no.3 s.58
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    • pp.135-140
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    • 2006
  • Nuclear factor-kappaB (NF-kappaB) is a critical transcription factor for maximal expression of many of the cytokines that are involved in the pathogenesis of inflammatory diseases. In this study, we found that 12 plant extracts among 200 plants, namely, Forsythia koreana, Capsicum annuum L, Mentha arvenis, Duchesnea chrysantha, Morus alba, Saururus Chinenis (Lour) Baill, Pine needle, Zingiber mioga (Thunb.), Roscoe, Houttuynia, Prunus yedoenis, Sasa quelpaertenis, significantly inhibited LPS- induced NF-kappaB activation in a concentration-dependent manner. Additionally, 12 plant extracts were found to have antioxidant activities in DPPH assay Therefore, we have attempted to determine whether 12 herbal extracts could inhibit the expression of cytokines possessing NF-kappaB promoter in their promoter regions. Consistently 12 herbal extracts inhibited LPS-induced production of TNF alpha and interleukin-8 (IL-8). These results show that 12 herbal extracts suppresses the production of pro-inflammatory mediators through the inhibition of the NF-kappaB signaling pathway, we suggest that 12 herbal extracts can be used as a anti-inflammatory and soothing agent.

Immuno-Modulatory Activities of Polysaccharides separated from Chrysanthemum zawadskii var. latilobum in Macrophage Cells (구절초(Chrysanthemum zawadskii var. latilobum)에서 분리된 다당류의 대식세포 면역조절 활성)

  • Sung, Nak-Yun;Park, Yoo-Young;Kim, Yi-Eun;Cho, Eun-Ji;Kim, Mi-Hwan;Ryu, Gi-Hyung;Byun, Eui-Hong;Park, Youn-Je
    • The Korean Journal of Food And Nutrition
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    • v.29 no.3
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    • pp.431-437
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    • 2016
  • Macrophages play a pivotal role in the innate and adaptive immune systems. This study investigated the immuno-modulatory activities of polysaccharides separated from Chrysanthemum zawadskii var. latilobum (CZPS) in macrophages. Polysaccharides from Chrysanthemum zawadskii var. latilobum were extracted by the ethanol precipitation method. RAW 264.7 mouse macrophage cell line was treated with CZPS (4 to $128{\mu}g/mL$), and there was no cytotoxicity at a dose below $32{\mu}g/mL$. The levels of nitric oxide (NO) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-6, IL-$1{\beta}$) production in the CZPS treated group ($32{\mu}g/mL$) were $6.5{\pm}0.12{\mu}m$ (NO), $1252.8{\pm}79.85$ (TNF-${\alpha}$), $305.4{\pm}29.41$ (IL-6), and $683.3{\pm}59.71$ (IL-$1{\beta}$), respectively, and they were significantly increased when compared to the control group; $2.2{\pm}0.03{\mu}m$ (NO), $452.3{\pm}38.34$ (TNF-${\alpha}$), $31.7{\pm}5.75$ (IL-6), and $184.1{\pm}11.52$ (IL-$1{\beta}$). Additionally, protein expression of inducible nitric oxide synthase (iNOS) and phosphorylation of MAPKs and NF-${\kappa}B$ expression were significantly increased upon CZPS treatment. Therefore, these results indicated that polysaccharides separated from Chrysanthemum zawadskii var. latilobum (CZPS) may have a potential immunomodulatory activity in macrophages through MAPKs and NF-${\kappa}B$ signaling, and this information is useful for the development of immune enhancing adjuvant materials using a natural ingredient.

Effect of Angelicae Gigantis Radix for Inflammatory Response in HaCaT Cells (당귀(當歸) 추출물이 피부 각질형성세포의 염증반응에 미치는 영향)

  • Huh, Jung;Park, Hoyeon;Kim, Eom Ji;Kim, Eun-Young;Sohn, Youngjoo;Jung, Hyuk-Sang
    • The Korea Journal of Herbology
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    • v.37 no.3
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    • pp.9-19
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    • 2022
  • Objectives : Angelicae Gigantis Radix (AG) is a plant of the Ranunculus family. AG have been reported to have various pharmacological effects on human health which include uterine growth promotion, anti-inflammatory, analgesic, and immune enhancement. However, research on dermatitis disease is insufficient. Therefore, we investigated the effects of AG on tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ) stimulated HaCaT cell. Methods : To investigate the effect of AG on HaCaT cell, HaCaT cells were pre-treated with AG for 1 hour and then stimulated with TNF-α/IFN-γ. After 24 hours, media and cells were harvested to analyze the inflammatory mediators. Concentration of human interleukin-1beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and TNF-α in the media were assessed by ELISA. mRNA expression of human thymus and activation-regulated chemokine (TARC), IL-6, and IL-8 were analyzed by RT-PCR. Additionally, the mechanisms of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway were investigated by Western blot. Results : The treatment of AG inhibited gene expression levels of IL-6, IL-8, and TARC and protein expression levels of IL-1β, MCP-1, and GM-CSF. Also, AG significantly reduced extracellular signal-regulated kinase (ERK) phosphorylation and NF-κB translocation in TNF-α/IFN-γ stimulated HaCaT cell. Conclusions : Taken together, these results demonstrate that AG can alleviate inflammatory diseases such as atopic dermatitis by regulating the expression of inflammatory cytokines. Also, it suggest that AG may a promising candidate drug for the treatment of inflammatory disease such as atopic dermatitis.

Leptin, adiponectin, interleukin-6 and tumor necrosis factor-α in obese adolescents (비만아에서의 leptin, adiponectin, interleukin-6, tumor necrosis factor-α에 대한 연구)

  • Gil, Joo Hyun;Lee, Jung Ah;Kim, Ji Young;Hong, Young Mi
    • Clinical and Experimental Pediatrics
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    • v.51 no.6
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    • pp.597-603
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    • 2008
  • Purpose : Obesity is associated with insulin resistance. Insulin resistance and the presence of pro-inflammatory mediators are thought to cause a state of vascular endothelial dysfunction, an abnormal lipid profile, hypertension, and vascular inflammation. These chronic inflammatory responses, which are characterized by abnormal cytokine production, lead to activation of a pro-inflammatory signaling pathway. Leptin is an important mediator of inflammatory processes and immune-mediated diseases. The purpose of this study was to investigate the relationship between leptin and various cytokines associated with obesity in adolescents. Methods : Sixty-six obese adolescents (between 16-17 years of age, obesity index >130%) and 26 normal controls were included in this study. Obesity index and body mass index (BMI) were calculated. Serum lipid profile, AST and ALT were tested after 10 hours of fasting. Tumor necrosis factor alpha (TNF-${\alpha}$) and Interleukin-6 (IL-6) levels were measured by ELISA. Insulin, adiponectin, and leptin levels were estimated by radioimmunoassay. Results : Leptin was significantly higher in the obese adolescents compared to the control adolescents ($12.0{\pm}6.8ng/mL$ vs $6.3{\pm}1.0ng/mL$). TNF-${\alpha}$, IL-6, and insulin were significantly higher in the obese adolescents. Adiponectin was significantly lower in the obese group than the control group ($3.3{\pm}1.9{\mu}g/mL$ vs $5.0{\pm}1.4{\mu}g/mL$). Leptin had positive correlations with obesity index, BMI, and IL-6. Conclusion : In obese adolescents, leptin, TNF-${\alpha}$, IL-6, and insulin might be important mediators of obesity. Further clinical research is necessary to ascertain leptin as a predictor of cardiovascular diseases and to develop a guideline for clinical intervention.

Eleocharis kuroguwai Ohwi Ameliorates LPS-mediated Inflammation by Suppressing MAPKs Signaling (LPS로 유도된 염증 상태 내에서 MAPKs 세포신호 전달체계를 저해하는 올방개의 항염증 효과)

  • Kim, Kang-Hoon;Bae, Eun Young;Lim, Hyun Goo;Kim, Mi Heui;Oh, Tae-Seok;Lee, Seung Woong
    • Journal of Life Science
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    • v.30 no.5
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    • pp.476-482
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    • 2020
  • In rice agriculture, Eleocharis kuroguwai Ohwi (olbanggae) is a target for herbicidal intervention as a problem weed although it has also long been used clinically as a traditional medicine for jaundice, fever, and blood flow. E. kuroguwai has been evaluated in many clinical trials, but its molecular biological advantages are still unknown. Here, we investigate the anti-inflammatory effects of E. kuroguwai 80% ethanol extracts by screening NO production in LPS-induced macrophage activation. To find the most effective fractions, we partitioned five sub-fractions using HP20 column chromatography, namely 20%, 40%, 60%, 80%, and 100%. Of these, the 60% and 80% sub-fractions were found to significantly inhibit NO production; there were no toxicological effects at any concentration. In addition, the 80% sub-fraction inhibited significantly the iNOS and the mRNA of the pro-inflammatory mediators IL-6, TNF-α, and IL-1β by inhibiting the phosphorylation of JNK and ERK pathways associated with MAPKs signaling. Our results suggest that the 80% E. kuroguwai sub-fraction has the most significant anti-inflammatory effects of inhibiting iNOS and pro-inflammatory mediators and suppressing the phosphorylation of JNK and ERK. Therefore, the 80% sub-fraction of E. kuroguwai extract may be a therapeutic candidate for inflammatory diseases associated with the overexpression of MAPKs.

Anti-oxidant and Anti-inflammatory Effects of Ethanol Extracts from Aerial Part of Coriandrum sativum L. (고수(Coriandrum sativum L.) 지상부 추출물의 항산화 및 항염증 활성 효과)

  • Nan, Li;Lee, Chang-Hyun;Choi, You-Na;Choo, Byung-Kil
    • Korean Journal of Organic Agriculture
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    • v.27 no.4
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    • pp.513-528
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    • 2019
  • Coriandrum sativum L., an annual herbaceous plant of Apiaceae family. The present study evaluated the anti-oxidant activities and anti-inflammatory effects of ethanol extracts of C. sativum. The anti-oxidant activities of C. sativum were measured by total contents of polyphenol, flavonoid, DPPH and ABTS radical scavenging and reducing power activity. And anti-inflammatory effects of C. sativum were measured by LPS-induced RAW 264.7 cells. The results showed that the contents of total polyphenol and flavonoid were 76.03 ± 1.36 mg of gallic acid equivalents/g and 182.23 ± 4.32 mg of rutin equivalents/g at concentration 1 mg/mL of C. sativum. The DPPH radical scavenging activity was found to be 52.8% at 500 ㎍/mL. The ABTS radical scavenging activity was shown in 58.3% after exposure to 1,000 ㎍/mL. Reducing power activity was found to be 66.8% at 2,000 ㎍/mL. The inhibitory effect of NO production was found to be 65% concentration 500 ㎍/mL. In the generation quantity of inflammatory cytokines such as TNF-α and IL-1β in cell culture medium, the expression levels of inflammatory proteins in cells were showed decrease with the increase of concentration. Therefore, we suggest that the C. sativum should be a potential source of alternative anti-inflammatory drug with good anti-inflammatory effects.

Alteration of Stress Fiber in Fibroblastic Reticular Cells via Lymphotoxin β Receptor Stimulation is Associated with Myosin (Lymphotoxin β 수용체를 통한 fibroblastic reticular cell의 stress fiber 변화와 myosin의 연관성)

  • Kim, Min Hwan;Kim, Yeon Hee;Choi, Woobong;Lee, Jong-Hwan
    • Journal of Life Science
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    • v.25 no.5
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    • pp.585-593
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    • 2015
  • Stress fiber (SF) alteration is mediated by cellular receptors, which, upon interaction with the extracellular counterpart, signal to the actin cytoskeleton for remodeling. This association is mediated by a variety of scaffold and signaling factors, which control the mechanical and signaling activities of the interaction site. The heterotrimeric transmembrane lymphotoxin α1β2 (LTα1β2), a member of the tumor necrosis factor (TNF) family of cytokines, including soluble homotrimeric lymphotoxin (LT α), plays an important role in lymphoid tissue architecture. Ligation between LTα1β2 and the lymphotoxin β receptor (LTβR) activates signal-cascade in fibroblastic reticular cells (FRCs). We found LTβR stimulation using an agonistic anti-LTβR antibody alone or combined with LTα or TNFα induced changes in the actin and plasticity of cells. To clarify the involvement of myosin underlying the alteration, we analyzed the effect of myosin light chain kinase (MLCK) with an MLCK inhibitor (ML7), the phosphorylation level of myosin light chains (MLC), and the level of phospho-myosin phosphatase target subunit 1 (MYPT1) after treatment with an agonistic anti-LTβR antibody for cytoskeleton reorganization in FRCs. The inhibition of MLCK activity induced changes in the actin cytoskeleton organization and cell morphology in FRC. In addition, we showed the phosphorylation of MLC and MYPT1 was reduced by LTβR stimulation in cells. A DNA chip revealed the LTβR stimulation of FRC down-regulated transcripts of myosin and actin components. Collectively, these results suggest LTβR stimulation is linked to myosin regarding SF alteration in FRC.

Detrimental effects of lipopolysaccharides on maturation of bovine oocytes

  • Zhao, Shanjiang;Pang, Yunwei;Zhao, Xueming;Du, Weihua;Hao, Haisheng;Zhu, Huabin
    • Asian-Australasian Journal of Animal Sciences
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    • v.32 no.8
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    • pp.1112-1121
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    • 2019
  • Objective: Gram-negative bacteria lipopolysaccharide (LPS) has been reported to be associated with uterine impairment, embryonic resorption, ovarian dysfunction, and follicle retardation. Here, we aimed to investigate the toxic effects of LPS on the maturation ability and parthenogenetic developmental competence of bovine oocytes. Methods: First, we developed an in vitro model to study the response of bovine cumulusoocyte complexes (COCs) to LPS stress. After incubating germinal vesicle COCs in $10{\mu}g/mL$ of LPS, we analyzed the following three aspects: the expression levels of the LPS receptor toll-like receptor 4 (TLR4) in COCs, activities of intracellular signaling protein p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-kappa B (NF-${\kappa}B$); and the concentrations of interleukin (IL)-$1{\beta}$, tumor necrosis factor (TNF)-${\alpha}$, and IL-6. Furthermore, we determined the effects of LPS on the maturation ability and parthenogenetic developmental competence of bovine oocytes. Results: The results revealed that LPS treatment significantly elevated TLR4 mRNA and protein expression levels in COCs. Exposure of COCs to LPS also resulted in a marked increase in activity of the intracellular signaling protein p-p38 MAPK and NF-${\kappa}B$. Furthermore, oocytes cultured in maturation medium containing LPS had significantly higher concentrations of the proinflammatory cytokines IL-$1{\beta}$, TNF-${\alpha}$, and IL-6. LPS exposure significantly decreased the first polar body extrusion rate. The cytoplasmic maturation, characterized by polar body extrusion and distribution of peripheral cortical granules, was significantly impaired in LPS-treated oocytes. Moreover, LPS exposure significantly increased intracellular reactive oxygen species levels and the relative mRNA abundance of the antioxidants thioredoxin (Trx), Trx2, and peroxiredoxin 1 in oocytes. Moreover, the early apoptotic rate and the release of cytochrome C were significantly increased in response to LPS. The cleavage, morula, and blastocyst formation rates were significantly lower in parthenogenetically activated oocytes exposed to LPS, while the incidence of apoptotic nuclei in blastocysts was significantly increased. Conclusion: Together, these results provide an underlying mechanism by which LPS impairs maturation potential in bovine oocytes.