• Title/Summary/Keyword: nuclear protein

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Anti-inflammatory effects of Ishige sinicola ethanol extract in LPS-induced RAW 264.7 cell and mouse model (LPS로 유도된 RAW 264.7 Cell과 마우스 모델에 대한 넓패(Ishige sinicola) 에탄올 추출물의 항염증 효과)

  • Kim, Ji-Hye;Kim, Min-Ji;Kim, Koth-Bong-Woo-Ri;Park, Sun-Hee;Cho, Kwang-Su;Kim, Go-Eun;XU, Xiaotong;Lee, Da-Hye;Park, Ga-Ryeong;Ahn, Dong-Hyun
    • Food Science and Preservation
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    • v.24 no.8
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    • pp.1149-1157
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    • 2017
  • Inflammation is the first response of the immune system to infection or irritation in our body. The use of medicinal plants has been widely applied as an alternative source for drug development. One of marine natural resources, the anti-inflammatory effect of Ishige sinicola ethanol extract (ISEE), was evaluated by using LPS-induced RAW 264.7 cell and mice model. As a result, the production of nitric oxide (NO) and pro-inflammatory cytokines (IL-6, IL-$1{\beta}$, TNF-${\alpha}$) were inhibited with increasing concentration of ISEE without any cytotoxicity. Furthermore, ISEE suppressed the expression of not only inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-${\kappa}B$) p65, and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK) 1/2, p38, and c-Jun N-terminal kinase (JNK) in a dose-dependent manner. In mice ear edema test, the formation of edema was reduced at the highest dosage of ISEE and the reduction of the number of infiltrated mast cells was observed in histological analysis. These results indicate that ISEE has a potent anti-inflammatory activity and can be used as a pharmaceutical material for many kinds of inflammatory disease.

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.

Anti-inflammatory Activities of Ethanol Extracts of Dried Lettuce (Lactuca sativa L.) (건조 상추 에탄올 추출물의 항염증 활성)

  • Lee, Eun-Joo;Seo, Yu-Mi;Kim, Yong-Hyun;Chung, Chungwook;Sung, Hwa-Jung;Sohn, Ho-Yong;Park, Jong-Yi;Kim, Jong-Sik
    • Journal of Life Science
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    • v.29 no.3
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    • pp.325-331
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    • 2019
  • Lettuce (Lactuca sativa L.) is one of the most popular green leafy vegetables, and it contains various beneficial components including polyphenolic compounds and has been known to possess various biological functions such as anti-microbial, anti-oxidative, and anti-inflammatory activities. In the present study, we prepared ethanol extract of dried lettuce (DLE) and investigated its anti-inflammatory activity. To evaluate the anti-inflammatory activity of DLE, nitric oxide (NO) production was measured in LPS-activated mouse macrophage RAW 264.7 cells. DLE significantly suppressed NO production in these cells without affecting cell viabilities while resveratrol was used as a positive control. DLE dramatically decreased the expression of pro-inflammatory genes such as iNOS and COX-2 at the mRNA and protein levels and reduced the expression of several cytokines including $IL-1{\alpha}$, $IL-1{\beta}$, IL-1F6, $TNF-{\alpha}$, CSF2 and CXCL10. In addition, DLE suppressed phosphorylation of MAPKs and the nuclear translocation of $NF-{\kappa}B$ p65 indicating DLE shows its anti-inflammatory activity via regulating MAPKs pathway and $NF-{\kappa}B$ pathways. And also, DLE reduced the production of reactive oxygen species in a dose-dependent manner. DLE increased HO-1 protein expression, and also increased the nuclear translocation of Nrf2. Overall, our results suggest that lettuce down-regulate various pro-inflammatory genes and have its anti-inflammatory activity via regulating MAPKs, $NF-{\kappa}B$, and Nrf2/HO-1 pathways.

Anti-inflammatory Effect of Heat-Killed Enterococcus faecalis, EF-2001 (열처리 사균체 엔테로코커스 패칼리스 EF-2001의 항염증 효과)

  • Choi, Moon-Suk;Chang, Sang-Jin;Chae, Yuri;Lee, Myung-Hun;Kim, Wan-Joong;Iwasa, Masahiro;Han, Kwon-Il;Kim, Wan-Jae;Kim, Tack-Joong
    • Journal of Life Science
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    • v.28 no.11
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    • pp.1361-1368
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    • 2018
  • Inflammation is the most common condition in the human body. Tissue damage triggers inflammation, together with vasodilation and increased blood flow at the inflamed site, resulting in edema. Inflammatory responses are also triggered by lipopolysaccharide (LPS), a Toll-like receptor Enterococcus faecalis, a gram-positive organism, has been reported to possess immunomodulatory and preventive activities; however, its use may present risks of sepsis and other systemic infections. Heat-killed Enterococcus faecalis (EF-2001) has been reported to induce antitumor activity, but its effects on inflammation are not known. In the present study, we investigated the effect of EF-2001 on LPS-induced macrophage inflammatory responses. EF-2001 treatment reduced nitric oxide (NO) production, indicating suppression of inflammatory reactions. EF-2001 showed no cytotoxicity in macrophages. Further investigation of the anti-inflammatory mechanism of EF-2001 indicated that EF-2001 reduced the LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2. EF-2001 also reduced f the LPS induction of several inflammatory molecules involved in the nuclear factor-${\kappa}B$ ($NF-{\kappa}B$) and mitogen-activated protein kinase pathways, including ERK, JNK, and p38 phosphorylation, in a concentration-dependent manner. Additionally, EF-2001 inhibited Akt phosphorylation and increased the expression of the inhibitory ${\kappa}B$ ($I{\kappa}B$) protein, an inhibitor of $NF-{\kappa}B$. EF-2001 also inhibited the nuclear translocation of p65. These results suggest that EF-2001 has anti-inflammatory properties and may be useful for treating inflammatory diseases.

Proanthocyanidins Suppresses Lipopolysaccharide-stimulated Inflammatory Responses via Heme Oxygenase-1 Induction in RAW264.7 Macrophages (프로안토시아니딘의 항염증효과)

  • Cheon, Hye-Jin;Park, Sun Young;Jang, Hee-Ji;Cho, Da-Young;Jung, Jiwon;Park, Gimin;Jeong, Kyeong Mi;Kim, Jin-Kyung
    • Journal of Life Science
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    • v.29 no.4
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    • pp.484-491
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    • 2019
  • Proanthocyanidins are naturally occurring polyphenolic compounds abundant in many vegetables, plant skins (rind/bark), seeds, flowers, fruits, and nuts. Numerous in vitro and in vivo studies have demonstrated myriad effects potentially beneficial to human health, such as antioxidation, immunomodulation, DNA repair, and antitumor activity. Among immune cells, macrophages are crucial players in a variety of inflammatory responses to environmental conditions. However, it has been widely reported that macrophages cause chronic inflammation and are involved in a variety of diseases, such as obesity, diabetes, metabolic syndrome, and cancer. In this study, we report the suppressive effect of proanthocyanidins via the heme oxygenase-1 (HO-1)-related system, on the immune response of the LPS-stimulated mouse macrophage cell line RAW264.7. Increased HO-1 expression at mRNA and protein levels were found in proanthocyanidins-treated RAW264.7 cells. Further, proanthocyanidins enhanced nuclear factor-erythroid 2-related factor 2 translocation into the nucleus. RAW264.7 cells were treated with lipopolysaccharide (LPS) with or without proanthocyanidins, and inflammatory mediator expression levels were assessed. Proanthocyanidins treatment resulted in the attenuation of nitric oxide production and inducible nitric oxide synthase expression in LPS-stimulated RAW264.7 cells. In addition, mRNA and protein expression of proinflammatory cytokines, such as tumor necrosis factor-${\alpha}$ and interleukin-6, was inhibited by proanthocyanidins treatment in LPS-stimulated RAW264.7 cells. These findings support proanthocyanidins as a promising anti-inflammatory agent.

High-mobility Group Box 1 Induces the Epithelial-mesenchymal Transition, Glycolytic Switch, and Mitochondrial Repression via Snail Activation (HMGB1/Snail cascade에 의한 epithelial-mesenchymal transition 및 glycolytic switch, mitochondrial repression 유도)

  • Lee, Su Yeon;Ju, Min Kyung;Jeon, Hyun Min;Kim, Cho Hee;Park, Hye Gyeong;Kang, Ho Sung
    • Journal of Life Science
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    • v.29 no.11
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    • pp.1179-1191
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    • 2019
  • Cancer cells undergo the epithelial-mesenchymal transition (EMT) and show unique oncogenic metabolic phenotypes such as the glycolytic switch (Warburg effect) which are important for tumor development and progression. The EMT is a critical process for tumor invasion and metastasis. High-mobility group box 1 (HMGB1) is a chromatin-associated nuclear protein, but it acts as a damage-associated molecular pattern molecule when released from dying cells and immune cells. HMGB1 induces the EMT, as well as invasion and metastasis, thereby contributing to tumor progression. Here, we show that HMGB1 induced the EMT by activating Snail. In addition, the HMGB1/Snail cascade was found induce a glycolytic switch. HMGB1 also suppressed mitochondrial respiration and cytochrome c oxidase (COX) activity by a Snail-dependent reduction in the expression of the COX subunits COXVIIa and COXVIIc. HMGB1 also upregulated the expression of several key glycolytic enzymes, including hexokinase 2 (HK2), phosphofructokinase-2/fructose-2,6-bisphosphatase 2 (PFKFB2), and phosphoglycerate mutase 1 (PGAM1), in a Snail-dependent manner. However, HMGB1 was found to regulate some other glycolytic enzymes including lactate dehydrogenases A and B (LDHA and LDHB), glucose transporter 1 (GLUT1), and monocarboxylate transporters 1 and 4 (MCT1 and 4) in a Snail-independent manner. Transfection with short hairpin RNAs against HK2, PFKFB2, and PGAM1 prevented the HMGB1-induced EMT, indicating that glycolysis is associated with HMGB1-induced EMT. These findings demonstrate that HMGB1 signaling induces the EMT, glycolytic switch, and mitochondrial repression via Snail activation.

Usefulness of Stomach Extension after Drinking Orange Juice in PET/CT Whole Body Scan (PET/CT 전신 영상에서 오렌지 주스(Orange Juice)를 이용한 위장 확장 영상의 유용성)

  • Cho, Seok-Won;Chung, Seok;Oh, Shin-Hyun;Park, Hoon-Hee;Kim, Jae-Sam;Lee, Chang-Ho
    • The Korean Journal of Nuclear Medicine Technology
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    • v.13 no.1
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    • pp.86-92
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    • 2009
  • Purpose: The PET/CT has a clear distinction on the lesion of the functional image by adding anatomical information. It also could reduce the examination time using CT data as the attenuation-correction. When the stomach was contracted from a fast, it could bring a misinterpretation of the cancer of the lesion with a presence of physiological $^{18}F$-FDG uptake in stomach and it occasionally would bring an additional scan to confirm. To complement this shortcoming, the method that the patients had water before the examination to extend the stomach had been attempted. However, a short excretion time of the stomach did not give sufficiently extended image of the stomach. Then the patients had additional water and had the examination again. Therefore, the noticed fact is that the stomach excretion time depends on calories, protein content, and the level of carbohydrate. In this study, we use an orange juice to evaluate the extension of the stomach and usefulness of it. Materials and Methods: PET/CT scan were obtained on total 150 of patient from February 2008 to October2008, There were 3 groups in this study and each group had 50 patients. First group drank nothing, Second group drank water and third group drank orange juice. The patients (man 25, female 25) not drinking are the age of 30~71 years old (average: 54), the patients (man: 25, female: 25) drinking water (400 cc) are the age of 28~71 years old (average: 54) and the patients (man: 25, female: 25) drinking orange juice (400 cc) are the age of 32~74 years old (average: 56). The patients were fasted in 6-8 hours before the test, the patients were not diabetic. $^{18}F$-FDG 370~555 MBq were injected intravenously. The patients were in stable position for 1 hour, than the image was obtained. The patients drank water and other patients drank orange juice before Whole body scan. The image scan started from mid-femur to skull base. The emission scan acquired for three minutes per bed and the images were reconstructed. Stomach extension analysis is measured from vertical and horizontal length. Results: Stomach Extension was described as the vertical length of the Non Drink Group was $1.20{\pm}0.50\;cm$, horizontal length was $1.4{\pm}0.53\;cm$, the vertical length of the Water Drink Group was $1.67{\pm}0.63\;cm$, horizontal length was $1.65{\pm}0.77\;cm$, the vertical length of Orange juice Drink Group was $3.48{\pm}0.77\;cm$, horizontal length was $3.66{\pm}0.77\;cm$ in coronal image. Stomach Extension was described the vertical length of the Non Drink Group was $2.03{\pm}0.62\;cm$, horizontal length was $1.69{\pm}0.68\;cm$, the vertical length of Water Drink Group was $5.34{\pm}1.62\;cm$, horizontal length was $2.45{\pm}0.72\;cm$, the vertical length of Orange juice Drink Group was $7.74{\pm}1.62\;cm$, horizontal length was $3.57{\pm}0.77\;cm$ in transverse image. The Stomach Extension has specific differences (p<0.001). The SUVs shows the Non Drink Group were measured as Liver $2.52{\pm}0.42$, Lung $0.51{\pm}0.14$, the Water Drink Group were measured as Liver $2.47{\pm}0.38$, Lung $0.50{\pm}0.14$, Orange juice Drink Group were measured as Liver $2.47{\pm}0.38$, Lung $0.50{\pm}0.14$. The SUVs did not have specific differences (p>0.759). Conclusions: There was not a large difference of SUV in three groups. When the patients drank Orange juice and water, the range extension of stomach was higher than without drinking nothing and it was possible to acquire fully extended images. Therefore, it will be possible that unnecessary additional stomach scans will be reduced by drinking orange juice before the examination so that the patients' claim from uncomfortable and long period of fast will be minimized.

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Studies of the Effects of Acupuncture Stimulation at Huatuo Jiaji(EX B2) Points on Axonal Regeneration of Injured Sciatic Nerve in the Rats (화타협척혈 침자극에 의한 손상 말초신경의 재생효과에 관한 연구)

  • Kim, Dae-Feel;Park, Young-Hoi;Keum, Dong-Ho
    • Journal of Korean Medicine Rehabilitation
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    • v.18 no.4
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    • pp.39-61
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    • 2008
  • Objectives : The present study was performed to investigate whether acupuncture stimulation in the rats affected regeneration properties of the injured sciatic nerve. A differential effect of acupuncture stimulation on the one point near the spinal nerve root controlling sciatic nerve activity and the other point in the peripheral area subordinated by injured nerve was compared. Materials and Methods: Rat sciatic nerves were injured by crush, and the effects on axonal regeneration on injured sciatic nerves were evaluated by acupuncture stimulation at two different regions. In proximal acupuncture stimulation group, acupuncture stimulation was performed on Huatuo Jiaji(EX B2) points located from L5 to S1 vertebral levels to stimulate the nearest spinal nerve root that innervates sciatic nerves. In distal acupuncture stimulation group, acupuncture stimulation was performed on Zusanli(ST 36) and Weizhong(BL 40) points to stimulate at peripheral area dominated by injured sciatic nerves. Acupuncture stimulation was given every other days for 1 or 2 weeks. Sciatic nerve tissues collected from acupuncture stimulation experimental groups, injury control group, and intact animal group were used for protein analysis by Western blotting or Hoechst nuclear staining. To determine axonal regeneration, Dil fluorescence dye was injected into the sciatic nerve 0.5 cm distal to the injury site in individual animal groups and Dil-labeled cells by retrograde tracing were measured in the DRG at lumbar 5 or in the spinal cord. DRG sensory neurons prepared from individual animal groups were used to measure the extent of neurite outgrowth and for immunofluorescence staining with anti-GAP-43 antibody. Results : Animal groups given proximal or distal acupuncture stimulation showed upregulation of GAP-43 and Cdc2 protein levels in the sciatic nerve at 7 days after injury. Cdk2 protein levels were strongly induced by nerve injury, but did not show changes by acupuncture stimulation. Phospho-Erk1/2 protein levels were elevated by acupuncture stimulation above those present in the injury control animals. These increase in regeneration-associated protein levels appeared to be related with increase cell proliferation in the injured sciatic nerves. Hoechst 33258 staining of sciatic nerve tissue to visualize nuclei of individual cells showed increased Schwann cell number in the distal portion of the injured nerve 7 and 14 days after injury and further increases by acupuncture stimulation particularly at the proximal position. Measurement of axonal regeneration by retrograde tracing showed significantly increased Dil-labeled cells in proximal acupuncture stimulation group compared to distal acupuncture stimulation group and injury control group. Finally, an evaluation of axonal regeneration by retrograde tracing showed increased number of Dil labeled cells in the DRG at lumbar 5 or in the ventral horn of the spinal cord at lower thoracic level at 7 days after nerve injury. Conclusions : The present data show that the proximal acupuncture stimulation at Huatuo Jiaji(EX B2) points governing injured sciatic nerves was more effective for axonal regeneration than the distal acupuncture stimulation. Further studies on functional recovery or associated molecular mechanisms should be critical for developing animal models and clinical applications.

Action Mechanism of Antiestrogens on Uterine Growth in Immature Rats (자궁세포 성장에 미치는 항에스트로젠제의 작용기전)

  • Lee, Jung-Bin;Yoon, Mi-Chung;Kim, Chang-Mee;Hong, Sa-Suk;Ryu, Kyung-Za
    • The Korean Journal of Pharmacology
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    • v.26 no.2
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    • pp.167-176
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    • 1990
  • In the present study, we examined the effects of tamoxifen and LY117018 on various parameters for the estrogenic actions in order to understand the mechanism by which tamoxifen and LY117018 act on the uterine cells in 21-23 day old immature rats. Tamoxifen and LY117018 stimulated uterine weight and uterine contents of DNA, protein, and peroxidase activity in the absence of estradiol while inhibited above parameters in the presence of estradiol. Both cytosolic and nuclear progesterone receptors were increased by the treatment of tamoxifen and LY117018 as well as estradiol, but estradiol-induced increase in the progesterone receptors were reduced by the treatment of antiestrogens. These effects were enhanced by the multiple injections of antiestrogens. It seemed that tamoxifen was more agonistic than LY117018 but less antagonistic than LY117018, judged by their effects on various parameters for the estrogenic action. The affinities of estradiol, tamoxifen, and LY117018 for the estrogen receptor were $0.17{\pm}0.01nM(100%)$, $1.10{\pm}0.01nM(6.3%)$, and $0.23{\pm}0.01nM(77%)$, respectively. Furthermore, LY117018 was the competitive ligand for the estrogen receptor in dose-related manner but tamoxifen was not. Following estradiol treatment, nuclear estrogen receptor was sharply increased by 1 h, reaching the maximum by 16 h, while tamoxifen and LY117018 slightly increased nuclear estrogen receptor by 1 h and then decreased thereafter. It is therefore concluded that LY117018 is a competitive antagonist for the estrogen receptor with less estrogenic activity, compared to tamoxifen with low affinity to the estrogen receptor, and tamoxifen may act through other binding site than the estrogen receptor.

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Anti-Inflammmatiry Effects of Nerium indicum Ethanol Extracts through Suppression of NF-kappaB Activation (NF-κB 활성 저해를 통한 협죽도 에탄올 추출물의 항염증 효능)

  • Kim, Tae-Hwan;Ko, Seog-Soon;Park, Cheol;Park, Sang-Eun;Hong, Sang-Hoon;Kim, Byung-Woo;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.20 no.8
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    • pp.1221-1229
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    • 2010
  • Nerium indicum, an India-Pakistan-originated shrub belonging to the oleander family, is reported to possess many pharmacological activities including cardiac muscle stimulation, and anti-diabetes, anti-angiogenesis, anti-cancer and neuro-protective activities. However, the anti-inflammatory properties of N. indicum were unclear. In this study, we investigated the effects of ethanol extract of the N. indicum leaf and stem (ENIL and ENIS) on the expression of anti-inflammatory mediators in U937 human pre-monocytic cell models. In U937 cells stimulated with phorbol 12-myristate-13-acetate (PMA), pre-treatment with ENIS significantly inhibited the expression of both cyclooxygenase-2 (COX-2) mRNA and protein, which are associated with inhibition of the release of prostaglandin $E_2\;(PGE_2)$, whereas the inhibitory effects appeared weakly in ENIL. Moreover, ENIS significantly attenuated PMA-induced IkappaB ($I{\kappa}B$) degradation and suppressed elevated nuclear factor kappa B (NF-${\kappa}B$) nuclear translocation. Taken together, these findings provide important new insights that N. indicum exhibits anti-inflammatory properties by suppressing the transcription of pro-inflammatory cytokine genes through the NF-kB signaling pathway.