• Title/Summary/Keyword: Inflammatory mediator

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Resolvin D5, a Lipid Mediator, Inhibits Production of Interleukin-6 and CCL5 Via the ERK-NF-κB Signaling Pathway in Lipopolysaccharide-Stimulated THP-1 Cells

  • Chun, Hyun-Woo;Lee, Jintak;Pham, Thu-Huyen;Lee, Jiyon;Yoon, Jae-Hwan;Lee, Jin;Oh, Deok-Kun;Oh, Jaewook;Yoon, Do-Young
    • Journal of Microbiology and Biotechnology
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    • v.30 no.1
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    • pp.85-92
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    • 2020
  • One of the omega-3 essential fatty acids, docosahexaenoic acid (DHA), is a significant constituent of the cell membrane and the precursor of several potent lipid mediators. These mediators are considered to be important in preventing or treating several diseases. Resolvin D5, an oxidized lipid mediator derived from DHA, has been known to exert anti-inflammatory effects. However, the detailed mechanism underlying these effects has not yet been elucidated in human monocytic THP-1 cells. In the present study, we investigated the effects of resolvin D5 on inflammation-related signaling pathways, including the extracellular signal-regulated kinase (ERK)-nuclear factor (NF)-κB signaling pathway. Resolvin D5 downregulated the production of interleukin (IL)-6 and chemokine (C-C motif) ligand 5 (CCL5). Additionally, these inhibitory effects were found to be modulated by mitogen-activated protein kinase (MAPK) and NF-κB in lipopolysaccharide (LPS)-treated THP-1 cells. Resolvin D5 inhibited the LPS-stimulated phosphorylation of ERK and translocation of p65 and p50 into the nucleus, resulting in the inhibition of IL-6 and CCL5 production. These results revealed that resolvin D5 exerts anti-inflammatory effects in LPS-treated THP-1 cells by regulating the phosphorylation of ERK and nuclear translocation of NF-κB.

Shigella flexneri Inhibits Intestinal Inflammation by Modulation of Host Sphingosine-1-Phosphate in Mice

  • Kim, Young-In;Yang, Jin-Young;Ko, Hyun-Jeong;Kweon, Mi-Na;Chang, Sun-Young
    • IMMUNE NETWORK
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    • v.14 no.2
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    • pp.100-106
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    • 2014
  • Infection with invasive Shigella species results in intestinal inflammation in humans but no symptoms in adult mice. To investigate why adult mice are resistant to invasive shigellae, 6~8-week-old mice were infected orally with S. flexneri 5a. Shigellae successfully colonized the small and large intestines. Mild cell death was seen but no inflammation. The infected bacteria were cleared 24 hours later. Microarray analysis of infected intestinal tissue showed that several genes that are involved with the sphingosine-1-phosphate (S1P) signaling pathway, a lipid mediator which mediates immune responses, were altered significantly. Shigella infection of a human intestinal cell line modulated host S1P-related genes to reduce S1P levels. In addition, co-administration of S1P with shigellae could induce inflammatory responses in the gut. Here we propose that Shigella species have evasion mechanisms that dampen host inflammatory responses by lowering host S1P levels in the gut of adult mice.

Inhibition by Higenamine of Lipopolysaccharide-induced iNOS mRNA Expression and NO Production in Rat Aorta (Lipopolysaccharide로 활성화시킨 흰쥐 혈관의 iNOS 발현에 대한 Higenamine의 효과)

  • Kang Young-Jin;Lee Goun-Woo;Ku Eui-Bon;Lee Hoi-Young;Chang Ki-Churl
    • The Korean Journal of Physiology and Pharmacology
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    • v.1 no.3
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    • pp.297-302
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    • 1997
  • Higenamine was widely used as traditional remedy for the treatment of rhumatoid arthritis. Nitric oxide(NO) may be a critical mediator in this inflammatory disease. Synovial tissue from humans with inflammatory arthritis expresses NOS2(iNOS) mRNA and protein, and generates NO in vitro. We therefore, investigated the effect of higenamine on the induction of nitric oxide synthase(NOS) promoted by lipopolysaccharide(LPS). Prophylactic application of higenamine selectively prevented LPS-primed initiation of L-arginine-induced relaxation and restored rhenylephrine(PE)-induced contraction in rat aorta. LPS-stimulated nitrite production in the incubation medium was reduced by higenamine. Furthermore, RT-PCR and Northern analysis indicated that higenamine reduced iNOS expression primed by LPS in rat aorta. These results suggest that higenamine prevents LPS-promoted induction of NOS in vascular smooth muscle.

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Shiga Toxins Trigger the Secretion of Lysyl-tRNA Synthetase to Enhance Proinflammatory Responses

  • Lee, Moo-Seung;Kwon, Haenaem;Nguyen, Loi T.;Lee, Eun-Young;Lee, Chan Yong;Choi, Sang Ho;Kim, Myung Hee
    • Journal of Microbiology and Biotechnology
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    • v.26 no.2
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    • pp.432-439
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    • 2016
  • Shiga toxins (Stxs) produced by Shiga toxin-producing Escherichia coli (STEC) strains are major virulence factors that cause fatal systemic complications, such as hemolytic uremic syndrome and disruption of the central nervous system. Although numerous studies report proinflammatory responses to Stx type 1 (Stx1) or Stx type 2 (Stx2) both in vivo and in vitro, none have examined dynamic immune regulation involving cytokines and/or unknown inflammatory mediators during intoxication. Here, we showed that enzymatically active Stxs trigger the dissociation of lysyl-tRNA synthetase (KRS) from the multi-aminoacyl-tRNA synthetase complex in human macrophage-like differentiated THP-1 cells and its subsequent secretion. The secreted KRS acted to increase the production of proinflammatory cytokines and chemokines. Thus, KRS may be one of the key factors that mediate transduction of inflammatory signals in the STEC-infected host.

The Study on Pharmacological Activation as Cosmetic Material of Rosa rugosa Thunb. Flowers Extract (해당화꽃 추출물의 화장품소재로서 약리활성에 관한 연구)

  • Yu, Hye-Soo;Choi, Ji-Eun;Woo, Won-Hong;Mun, Yeun-Ja
    • Korean Journal of Acupuncture
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    • v.31 no.4
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    • pp.188-194
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    • 2014
  • Objectives : In this study, we investigated the effect of ethanol extract from Rosa rugosa Thunb. flowers(ERF) on the activities of antioxidant, antiwrinkle and whitening. Methods : We measured antioxidant efficacy of ERF by using 1,1-diphenyl-2-picrylhydrazyl(DPPH) assay. Also we confirmed the inhibitory effect of ERF on collagenase activity and melanin synthesis by using collagenase assay kit and dihydroxiphenylalanine staining, respectively. To evaluate the anti-inflammatory effects of ERF, we examined the inflammatory mediator IL-6. Results : ERF showed highly efficacy in DPPH radical scavenging activity. ERF dose-dependently suppressed collagenase activity. Ultraviolet-induced production of IL-6 decreased by ERF treatment. In B16F10 cell, ERF significantly reduced tyrosinase activity and melanin synthesis. Conclusions : From the above results, it was indicated that ERF could be utilized as anti-aging and whitening cosmetic ingredients.

Anti-inflammatory, Anti-glycation, Anti-tyrosinase and CDK4 Inhibitory Activities of Alaternin (=7-Hydroxyemodin)

  • Bhatarrai, Grishma;Choi, Jeong-Wook;Seong, Su Hui;Nam, Taek-Jeong;Jung, Hyun Ah;Choi, Jae Sue
    • Natural Product Sciences
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    • v.27 no.1
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    • pp.28-35
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    • 2021
  • The aim of this study was to anatomize the therapeutic potential of alaternin (=7-hydroxyemodin) against inflammation, advanced glycation end products (AGEs) formation, tyrosinase, and two cyclin-dependent kinases (CDKs), CDK2 and CDK4, and compare its potency with emodin. Alaternin showed lower cytotoxicity and higher dose-dependent inhibition against lipopolysaccharide (LPS) induced nitric oxide (NO) production with half maximal inhibitory concentration (IC50) of 18.68 µM. Similarly, alaternin efficaciously inhibited biotransformation of fluorescent AGEs and amyloid cross-β structure on the bovine serum albumin (BSA)-glucose-fructose system, five times more than emodin. Interestingly, alaternin also showed selective activity against CDK4 at 170 µM, whereas emodin inhibited both CDK2 and CDK4 at a concentration of 17 and 380 µM respectively. In addition, alaternin showed dose-dependent inhibitory activity against mushroom tyrosinase with inhibition percentage of 35.84 % at 400 µM. Altogether, alaternin with pronounced inhibition against inflammatory mediator (NO), glycated products formation, and targeted inhibition towards CDK4 receptor can be taken as an important candidate to target multiple diseases.

The influences of Phaseolus radiatus L.'s Ethanol Extracts and Fractions on Skin Whitening and Anti-inflammatory Effects (녹두(綠豆) 에탄올 추출물 및 분획물이 피부의 미백, 항염증 효과에 미치는 영향)

  • Lee, Yu-Lim;Choi, Jung-Hwa;Park, Soo-Yeon;Jeong, Min-Yeong;Lee, Ho-Chan;Song, Jie-Hye
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.31 no.3
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    • pp.39-49
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    • 2018
  • Objectives : This study is designed to clarify whitening, anti-inflammatory effect of fractions extracted from the mixture of Phaseolus radiatus L. and ethanol. Methods : In this experiment, we were intended to reveal whitening, anti-inflammatory effect of fractions extracted from the mixture of Phaseolus radiatus L. and ethanol. The whitening activity was confirmed by UV blocking activity, tyrosinase inhibiting activity, and melanin formation inhibiting activity. Anti-inflammatory activity is confirmed by measurement of cytotoxicity level by MTT assay and measurement of Cytokine expression, which is the main mediator of inflammation reaction. Results : As a results, overall activity was high in the ethyl acetate fraction. Tyrosinase inhibitory activity was less than 20% at all concentrations, but the activity to inhibit melanin self-production was higher than that of ethyl acetate fraction at $32.19{\pm}2.79%$ at $100{\mu}g/m{\ell}$. And ethyl acetate fraction had a relatively high UV blocking activity. In the anti-inflammatory test, the concentration-dependent activity was shown, and the chloroform and ethyl acetate fractions showed significant NO production inhibitory activity. Cytokine expression was superior to that of the final stage of B cell differentiation, and cell viability was over 80% except for the chloroform fraction at the concentration of $200{\mu}g/m{\ell}$. Conclusions : The results of this experiment confirmed the whitening effect and anti-inflammatory effect of Phaseolus radiatus L.'s extracts and fractions and report the possibility of application as external medicine.

Vaccinium bracteatum Thunb. Exerts Anti-Inflammatory Activity by Inhibiting NF-κB Activation in BV-2 Microglial Cells

  • Kwon, Seung-Hwan;Ma, Shi-Xun;Ko, Yong-Hyun;Seo, Jee-Yeon;Lee, Bo-Ram;Lee, Taek Hwan;Kim, Sun Yeou;Lee, Seok-Yong;Jang, Choon-Gon
    • Biomolecules & Therapeutics
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    • v.24 no.5
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    • pp.543-551
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    • 2016
  • This study was designed to evaluate the pharmacological effects of Vaccinium bracteatum Thunb. methanol extract (VBME) on microglial activation and to identify the underlying mechanisms of action of these effects. The anti-inflammatory properties of VBME were studied using lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. We measured the production of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase (COX)-2, prostaglandin $E_2$ ($PGE_2$), tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin-1 beta (IL-$1{\beta}$), and interleukin-6 (IL-6) as inflammatory parameters. We also examined the effect of VBME on intracellular reactive oxygen species (ROS) production and the activity of nuclear factor-kappa B p65 (NF-${\kappa}B$ p65). VBME significantly inhibited LPS-induced production of NO and $PGE_2$ and LPS-mediated upregulation of iNOS and COX-2 expression in a dose-dependent manner; importantly, VBME was not cytotoxic. VBME also significantly reduced the generation of the pro-inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, and IL-6. In addition, VBME significantly dampened intracellular ROS production and suppressed NF-${\kappa}B$ p65 translocation by blocking $I{\kappa}B-{\alpha}$ phosphorylation and degradation in LPS-stimulated BV2 cells. Our findings indicate that VBME inhibits the production of inflammatory mediators in BV-2 microglial cells by suppressing NF-${\kappa}B$ signaling. Thus, VBME may be useful in the treatment of neurodegenerative diseases due to its ability to inhibit inflammatory mediator production in activated BV-2 microglial cells.

Anti-Inflammatory Effects of Vegetable Soup in Murine Macrophage RAW 264.7 Cells (야채스프의 RAW 264.7 세포에서 항염증 효과)

  • Sim, Jae-Geun;Lee, Jae-Hyeok;Shin, Tae-Yong;Shin, Hye-Young;Jeong, Sook-Hee;Kim, Mi-Hye;Ku, Ho-Jun;Park, Jeong-Suk
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.8
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    • pp.1097-1101
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    • 2010
  • The aim of the present study is to investigate the anti-inflammatory effect of a vegetable soup (VS). The present study was designed to determine the effect of the vegetable soup on pro-inflammatory factors such as NO, iNOS and TNF-$\alpha$ in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The cell toxicity was determined by MTS assay. To evaluate the anti-inflammatory effect of vegetable soup, amount of NO was measured using the NO detection kit and the iNOS expression was measured by reverse transcriptase polymerase chain reaction (RT-PCR). Also, proinflammatory cytokines were measured by ELISA kit. The results showed that the vegetable soup reduced NO, iNOS and TNF-$\alpha$ production without cytotoxicity. Our results suggest that the vegetable soup may have an anti-inflammatory property through suppressing inflammatory mediator productions and appears to be useful to develop the functional food realted to anti-inflammation.

Anti-inflammatory effects of Chamaecyparis obtusa (Siebold & Zucc.) Endl. Leaf Fractions (편백(Chamaecyparis obtusa (Siebold & Zucc.) Endl.) 잎 분획물의 항염증 효과)

  • Yong-Jin Kwon
    • Journal of the Korean Applied Science and Technology
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    • v.40 no.6
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    • pp.1268-1277
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    • 2023
  • In this study, to evaluate the possibility of utilizing Chamaecyparis obtusa (Siebold & Zucc.) Endl. (C. obtusa) leaf fractions as anti-inflammatory functional materials, C. obtusa extract extracted with 99% ethanol (CO99EL) was fractionated with hexane (CO99EL-H), chloroform (CO99EL-C), ethyl acetate (CO99EL-E), butanol (CO99EL-B) and distilled water (CO99EL-W). The anti-inflammatory effects of each fraction was performed using lipopolysaccharide (LPS)-induced RAW264.7 mouse macrophages. Cytotoxicity was highest in CO99EL-H and CO99EL-C and lowest in CO99EL-W. Interestingly, LPS-induced iNOS expression and NO production were significantly reduced by CO99EL-H and CO99EL-E, and COX-2 expression was significantly reduced by CO99EL-B and CO99EL-W. In addition, interleukin (IL)-1𝛽, an inflammatory cytokine increased by LPS, was significantly reduced by CO99EL-C, CO99EL-E, CO99EL-B and CO99EL-W, and IL-6 was significantly reduced by CO99EL-B and CO99EL-W. Therefore, the janus kinase (JAK)/signaling transducer and activator of transcription (STAT) signaling pathway activated by LPS was significantly reduced by CO99EL-H and CO99EL-C, and the mitogen-activated protein kinase (MAPK) signaling pathway was slightly reduced by CO99EL-H and CO99EL-C. However, nuclear factor (NF)-𝜅B activity was not reduced by any fractions. Based on the results of this study, it was confirmed that CO99EL fractions have different anti-inflammatory mechanisms depending on the solvent used for fractionation.