• Title/Summary/Keyword: $I{\kappa}B-{\alpha}$ $NF-{\kappa}B$

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Effects of Low Dose Gamma Irradiation on the Inflammatory Response in Spleen Cells (저선량 감마선 노출에 의한 비장세포의 염증 유발 작용에 대한 연구)

  • Sohn, Eun-Hwa
    • KSBB Journal
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    • v.28 no.6
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    • pp.415-422
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    • 2013
  • Gamma irradiation (${\gamma}IR$) is widely used for radiotherapy as a treatment of cancer cells although it has a risk to damage normal cells. Inflammation is regarded as one of side effects of ${\gamma}IR$ while the effect of low dose of ${\gamma}IR$ on inflammation has not been researched well. Here, we investigated the inflammatory responses of low dose of ${\gamma}IR$ on murine spleen cells. It was evaluated if ${\gamma}IR$ affected the mitogen-induced lymphocyte proliferation, the regulation of various inflammatory cytokines (IFN-${\gamma}$, IL-2, IL-17, IL-4, IL-10), and the involvement of Ikaros and MAPK/NF-${\kappa}B$ medicated mechanism. Exposure of $^{137}Cs-{\gamma}IR$ below 2 Gy decreased the lymphocytes proliferative response to mitogens (LPS, ConA) except at the lowest dose, 0.05 Gy. IL-17, IL-2 and IL-4 mRNA increased at 0.5 and 2 Gy, but not altered at 0.05 Gy. IL-10, anti-inflammatory cytokine, increased only at 0.05 Gy. In regard to intracellular signaling, p-JNK, p-p38 and p-$I{\kappa}B{\alpha}$ were not changed, whereas the activation of ERK and Ikaros increased at the lowest dose. These results suggest that exposure of ${\gamma}IR$ less than 0.5 Gy (or below 0.05 Gy) has beneficial effects as a radiation hormesis on immune function.

Inhibitory Effect of Standardized Curcuma xanthorrhiza Supercritical Extract on LPS-Induced Periodontitis in Rats

  • Kook, Kyo Eun;Kim, Changhee;Kang, Wonku;Hwang, Jae-Kwan
    • Journal of Microbiology and Biotechnology
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    • v.28 no.10
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    • pp.1614-1625
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    • 2018
  • Periodontitis, which is a severe inflammatory disease caused by endotoxins secreted from oral pathogens, destructs gingival tissue and alveolar bone. Curcuma xanthorrhiza, commonly called Java turmeric, has been shown to possess anti-bacterial and anti-inflammatory activities. The present study evaluated the inhibitory effect of C. xanthorrhiza supercritical extract (CXS) standardized with xanthorrhizol on lipopolysaccharide (LPS)-induced periodontitis in an animal model. LPS was topically injected into the periodontium of Sprague-Dawley rats to induce periodontitis and CXS (30 and $100mg{\cdot}kg^{-1}{\cdot}day^{-1}$) was orally administered after day 12. Histologically, CXS inhibited the collapse of gingival tissue by preventing cell infiltration. CXS significantly downregulated the expression of matrix metalloproteases (MMPs) and inflammation-related biomarkers, such as nuclear factor-kappa B ($NF-{\kappa}B$) and interleukin-1 beta ($IL-1{\beta}$) in gingival tissue. CXS also improved bone remodeling by downregulating osteoclastic transcription factors, such as nuclear factor of activated T-cells c1 (NFATc1), tartrate-resistant acid phosphatase (TRAP), and cathepsin K. In addition, CXS upregulated osteoblast differentiation-related markers, alkaline phosphate (ALP) and collagen type I alpha (COLA1). Thus, CXS can ameliorate periodontitis by inhibiting inflammation and improving bone remodeling.

Inhibitory Effect of Curcumin on Nitric Oxide Production in Lipopolysaccharide-Stimulated RAW264.7 Cells and Its Suppressive Mechanism (대식세포주 RAW264.7 세포에서 Curcumin의 Lipopolysaccharide에 의한 Nitric Oxide 생성 억제 효과)

  • Lee, Yong-Gyu;Cho, Jae-Youl
    • Korean Journal of Medicinal Crop Science
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    • v.15 no.6
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    • pp.451-456
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    • 2007
  • Curcumin, a polyphenolic antioxidant purified from turmeric, has been known to possess various biological activities such as anti-oxidative, anti-inflammatory and anti-cancer effects. In this study, we have explored anti-inflammatory effect of curcumin using Gram (-) bacterium-derived endotoxin (lipopolysaccharide: LPS) and macrophage cell line RAW264.7. Curcumin suppressed NO production in LPS-activated RAW264.7 cells in a dose-dependent manner, Curcumin also blocked the activation of $NF-{\kappa}B$ but not AP-1 according to luciferase assay. Furthermore, this compound suppressed the phosphorylation of a series of intracellular signaling components such as Src, JAK-2, Akt, IKK and $I{\kappa}B{\alpha}$ under LPS stimulation in a time dependent manner, Therefore, our data suggest that curcumin was able to protect the host from Gram(-) bacterial-infection-mediated inflammatory symptoms.

The Review on the Study related to Anti-inflammatory Mechanism of Bee Venom Therapy (봉독요법(蜂毒療法)의 항염증(抗炎症) 기전(機轉) 연구(硏究)에 관(關)한 고찰(考察))

  • Choi, Jung-Sik;Park, Jang-Woo;Oh, Min-Seok
    • Journal of Haehwa Medicine
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    • v.15 no.1
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    • pp.141-160
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    • 2006
  • The obtained results are summarized as follows 1. New findings are reporting year by year as for the study related to Anti-inflammatory mechanism of Bee Venom therapy. 2. The Anti-inflammatory effect of Bee Venom therapy is achieved through counterirritation, stimulations to adrenal cortex, immuno-regulation, antioxidation, removal of free radicals, modulation of AGP gene induction. 3. The chief components of Bee Venom related to Anti-inflammatory effect are Melittin, MCD peptide, Apamin, Adolapin etc. 4. Melittin binds to secretory phospholipase A2 and inhibits its enzymatic activity. 5. Melittin blocks neutophil O2-production. 6. MCD peptide(Peptide 401) stimulates the mast cell secrets histamine, Anti-inflammatory effect caused by this is 'conterirritation'. 7. Melittin & Apamin have an anti-inflammatory effect by inducing cortisone secretion. 8. MCD peptide & Apamin increase immunologic fuction by stimulating hypophysis & adrenal cortex and have an anti-inflammatory effect by inhibiting synthesis of prostaglandin from arachidonic acid. 9. Adolapin have an anti-inflammatory effect by inhibiting COX. 10. Bee Venom have an anti-inflammatory effect by suppressing AGP($\alpha$-acid glycoprotein). 11. Bee Venom have an anti-inflammatory effect by inhibiting NO, iNOS, PLA2, COX-2, TNF-$\alpha$, IL-1, NF-${\kappa}B$, MAP kinase.

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Intestinal anti-inflammatory activity of Sasa quelpaertensis leaf extract by suppressing lipopolysaccharide-stimulated inflammatory mediators in intestinal epithelial Caco-2 cells co-cultured with RAW 264.7 macrophage cells

  • Kim, Kyung-Mi;Kim, Yoo-Sun;Lim, Ji Ye;Min, Soo Jin;Ko, Hee-Chul;Kim, Se-Jae;Kim, Yuri
    • Nutrition Research and Practice
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    • v.9 no.1
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    • pp.3-10
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    • 2015
  • BACKGROUND/OBJECTIVES: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract. Previously, Sasa quelpaertensis leaves have been shown to mediate anti-inflammation and anti-cancer effects, although it remains unclear whether Sasa leaves are able to attenuate inflammation-related intestinal diseases. Therefore, the aim of this study was to investigate the anti-inflammatory effects of Sasa quelpaertensis leaf extract (SQE) using an in vitro co-culture model of the intestinal epithelial environment. MATERIALS/METHODS: An in vitro co-culture system was established that consisted of intestinal epithelial Caco-2 cells and RAW 264.7 macrophages. Treatment with lipopolysaccharide (LPS) was used to induce inflammation. RESULTS: Treatment with SQE significantly suppressed the secretion of LPS-induced nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), IL-6, and IL-$1{\beta}$ in co-cultured RAW 264.7 macrophages. In addition, expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and tumor necrosis factor (TNF)-${\alpha}$ were down-regulated in response to inhibition of $I{\kappa}B{\alpha}$ phosphorylation by SQE. Compared with two bioactive compounds that have previously been identified in SQE, tricin and P-coumaric acid, SQE exhibited the most effective anti-inflammatory properties. CONCLUSIONS: SQE exhibited intestinal anti-inflammatory activity by inhibiting various inflammatory mediators mediated through nuclear transcription factor kappa-B (NF-kB) activation. Thus, SQE has the potential to ameliorate inflammation-related diseases, including IBD, by limiting excessive production of pro-inflammatory mediators.

Anti-Inflammatory Effect of Rosa rugosa Flower Extract in Lipopolysaccharide-Stimulated RAW264.7 Macrophages

  • Tursun, Xirali;Zhao, Yongxin;Talat, Zulfiya;Xin, Xuelei;Tursun, Adila;Abdulla, Rahima;AkberAisa, Haji
    • Biomolecules & Therapeutics
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    • v.24 no.2
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    • pp.184-190
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    • 2016
  • Rosa rugosa Thunb, a deciduous shrub of the genus Rosa, has been widely used to treat stomach aches, diarrhoea, pain, and chronic inflammatory disease in eastern Asia. In recent years, our research team has extensively studied the Rosa rugosa flower extract, and specifically undertook pharmacological experiments which have optimized the extraction process. Our methods have yielded a standard extract enriched in phenolic compounds, named PRE. Herein, we expand our efforts and evaluated the anti-inflammatory activity of PRE on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. PRE significantly inhibited production of nitric oxide (NO), prostaglandin $E_2(PGE_2)$, tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, and interleukin $1{\beta}$ (IL-$1{\beta}$), as well as expression of their synthesizing enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase2 (COX-2). Furthermore, PRE inhibited activity of mitogen-activated protein kinases (MAPK) as well as nuclear factor-kappa B (NF-${\kappa}B$) signaling pathway. Our findings are the first to explain the anti-inflammatory mechanism by PRE in LPS-stimulated macrophages. Given these results, we propose that PRE has therapeutic potential in the prevention of inflammatory disorders.

Anti-inflammatory effect of barley leaf ethanol extract in LPS-stimulated RAW264.7 macrophage (LPS로 자극한 RAW264.7 대식세포에서 보리순 에탄올 추출물의 항염증 효과)

  • Kim, Mee-Kyung;Kim, Dae-Yong
    • Food Science and Preservation
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    • v.22 no.5
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    • pp.735-743
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    • 2015
  • This study investigated the anti-inflammatory activity of barley leaf extract in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and hairless mice. Pre-treatment with barley leaf extract significantly inhibited the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-II (COX-II) in a dose-dependent manner in LPS-stimulated RAW264.7 cells. Barley leaf extract also significantly inhibited the secretion of inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$), and interleukin-6 (IL-6). Moreover, phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear translocation of nuclear factor-kappa B (NF-${\kappa}B$) were strongly suppressed by barley leaf extract in LPS-stimulated cells. In hairless mice, barley extract significantly decreased the pathological phenotypes of contact dermatitis, such as erythema, edema, and scabs. These results indicate that barley leaf extract has an anti-inflammatory effect and therefore a possible role in the treatment of inflammatory diseases or in functional cosmetics.

Resveratrol raises in vitro anticancer effects of paclitaxel in NSCLC cell line A549 through COX-2 expression

  • Kong, Fanhua;Zhang, Runqi;Zhao, Xudong;Zheng, Guanlin;Wang, Zhou;Wang, Peng
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.5
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    • pp.465-474
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    • 2017
  • The aim of this study was to determine the raising anticancer effects of resveratrol (Res) on paclitaxel (PA) in non-small cell lung cancer (NSCLC) cell line A549. The $10{\mu}g/ml$ of Res had no effect on human fetal lung fibroblast MRC-5 cells or on A549 cancer cells and the 5 or $10{\mu}g/ml$ of PA also had no effect on MRC-5 normal cells. PA-L ($5{\mu}g/ml$) and PA-H ($10{\mu}g/ml$) had the growth inhibitory effects in NSCLC cell line A549, and Res increased these growth inhibitory effects. By flow cytometry experiment, after Res ($5{\mu}g/ml$)+PA-H ($10{\mu}g/ml$) treatment, the A549 cells showed the most apoptosic cells compared to other group treatments, and after additional treatment with Res, the apoptosic cells of both two PA concentrations were raised. Res+PA could reduce the mRNA and protein expressions of COX-2, and Res+PA could reduce the COX-2 related genes of VEGF, MMP-1, MMP-2, MMP-9, $NF-{\kappa}B$, Bcl-2, BclxL, procollagen I, collagen I, collagen III and CTGF, $TNF-{\alpha}$, $IL-1{\beta}$, iNOS and raise the TIMP-1, TIMP-2, TIMP-3, $I{\kappa}B-{\alpha}$, p53, p21, caspase-3, caspase-8, caspase-9, Bax genes compared to the control cells and the PA treated cells. From these results, it can be suggested that Res could raise the anticancer effects of PA in A549 cells, thus Res might be used as a good sensitizing agent for PA.

Anti-inflammatory effect of Lonicera caerulea through ATF3 and Nrf2/HO-1 Activation in LPS-stimulated RAW264.7 Cells

  • Kim, Ha Na;Park, Su Bin;Kim, Jeong Dong;Jeong, Jin Boo
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2019.10a
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    • pp.65-65
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    • 2019
  • In this study, we evaluated the anti-inflammatory effect of extracts of leaves (LCLE) and branches (LCBE) from L. caerulea in LPS-stimulated RAW264.7 cells. Inhibitory effect of LCLE and LCBE against LPS-induced overproduction of NO, iNOS and $IL-1{\beta}$ was higher than LCFE. Furthermore, LCLE and LCBE significantly inhibited the overexpression of COX-2, IL-6 and $TNF-{\alpha}$ in LPS-stimulated RAW264.7 cells. LCLE and LCBE did not inhibited LPS-induced degradation of $I{\kappa}B-{\alpha}$, but blocked the nuclear accumulation of p65. LCLE did not inhibited LPS-induced phosphorylation of ERK1/2 and p38, while LCBE significantly attenuated phosphorylation level of p38. LCLE and LCBE increased HO-1 protein level and decrease of iNOS and $IL-1{\beta}$ expression by LCLE and LCBE was inhibited by HO-1 knockdown. The inhibition of p38 by SB203580 and ROS by NAC blocked HO-1 expression by LCLE and LCBE. LCLE and LCBE increased p38 phosphorylation and the inhibition of ROS by NAC blocked p38 phosphorylation LCLE and LCBE. LCLE and LCBE induced nuclear accumulation of Nrf2, but this was significantly reversed by the inhibition of p38 and ROS. In addition, LCLE and LCBE increased ATF3 expression and decrease of iNOS and $IL-1{\beta}$ expression by LCLE and LCBE was inhibited by ATF3 knockdown. Collectively, LCLE and LCBE inhibited LPS-induced $NF-{\kappa}B$ activation by blocking p65 nuclear accumulation, increased HO-1 expression by ROS/p38/Nrf2 activation, and increased ATF3 expression. Furthermore, LCBE inhibited LPS-induced p38 phosphorylation.

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Inhibitory Activity of Cordyceps bassiana Extract on LPS-induced Inflammation in RAW 264.7 Cells by Suppressing NF-κB Activation

  • Yoon, Deok Hyo;Han, Changwoo;Fang, Yuanying;Gundeti, Shankariah;Han Lee, In-Sook;Song, Won O;Hwang, Ki-Chul;Kim, Tae Woong;Sung, Gi-Ho;Park, Haeil
    • Natural Product Sciences
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    • v.23 no.3
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    • pp.162-168
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    • 2017
  • Cordyceps bassiana has long been used as an oriental medicine and reported to possess diverse biological activities. The fruiting bodies of Cordyceps bassiana was extracted with ethanol and then further fractionated with n-hexane, ethyl acetate, n-butanol and water. The butanol fraction from Cordyceps bassiana (CBBF) exhibited the most effective in anti-inflammatory activity in RAW 264.7 macrophages and the roles of CBBF on the anti-inflammation cascade in LPS-stimulated RAW 264.7 cells were studied. To investigate the mechanism by which CBBF inhibits NO, iNOS and COX-2, the activation of $I{\kappa}B$ and MAPKs in LPS-activated macrophage were examined. Our present results demonstrated that CBBF inhibits NO production and iNOS expression in LPS-stimulated RAW 264.7 macrophage cells, and these effects were mediated through the inhibition of $I{\kappa}B-{\alpha}$, JNK and p38 phosphorylation. Also, CBBF suppressed activation of MAPKs including p38 and SAPK/JNK. Furthermore, CBBF significantly suppressed LPS-induced intracellular ROS generation. Its inhibition on iNOS expression, together with its antioxidant activity, may support its anti-inflammatory activity. Thus Cordyceps bassiana can be used as a useful medicinal food or drug for further studies.