• Title/Summary/Keyword: TNFa

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High Throughput Fluorogenic Assay for TNF-alpha Converting Enzyme(TACE) inhibitors

  • Keum, Se-Hoon;Lee, Bong-Yong
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.125.2-126
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    • 2003
  • Human tumor necrosis factor-alpha (TNFa) is a key pro-inflammatory cytokine produced by activated monocytes and macrophage as a part of the self-defence machinery. TNF-a converting enzyme (TACE) is the metalloproteinase that processes the membrane bound precursor of TNFa to the soluble component. (omitted)

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Inhalation of panaxadiol alleviates lung inflammation via inhibiting TNFA/TNFAR and IL7/IL7R signaling between macrophages and epithelial cells

  • Yifan Wang;Hao Wei;Zhen Song;Liqun Jiang;Mi Zhang;Xiao Lu;Wei Li;Yuqing Zhao;Lei Wu;Shuxian Li;Huijuan Shen;Qiang Shu;Yicheng Xie
    • Journal of Ginseng Research
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    • v.48 no.1
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    • pp.77-88
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    • 2024
  • Background: Lung inflammation occurs in many lung diseases, but has limited effective therapeutics. Ginseng and its derivatives have anti-inflammatory effects, but their unstable physicochemical and metabolic properties hinder their application in the treatment. Panaxadiol (PD) is a stable saponin among ginsenosides. Inhalation administration may solve these issues, and the specific mechanism of action needs to be studied. Methods: A mouse model of lung inflammation induced by lipopolysaccharide (LPS), an in vitro macrophage inflammation model, and a coculture model of epithelial cells and macrophages were used to study the effects and mechanisms of inhalation delivery of PD. Pathology and molecular assessments were used to evaluate efficacy. Transcriptome sequencing was used to screen the mechanism and target. Finally, the efficacy and mechanism were verified in a human BALF cell model. Results: Inhaled PD reduced LPS-induced lung inflammation in mice in a dose-dependent manner, including inflammatory cell infiltration, lung tissue pathology, and inflammatory factor expression. Meanwhile, the dose of inhalation was much lower than that of intragastric administration under the same therapeutic effect, which may be related to its higher bioavailability and superior pharmacokinetic parameters. Using transcriptome analysis and verification by a coculture model of macrophage and epithelial cells, we found that PD may act by inhibiting TNFA/TNFAR and IL7/IL7R signaling to reduce macrophage inflammatory factor-induced epithelial apoptosis and promote proliferation. Conclusion: PD inhalation alleviates lung inflammation and pathology by inhibiting TNFA/TNFAR and IL7/IL7R signaling between macrophages and epithelial cells. PD may be a novel drug for the clinical treatment of lung inflammation.

Association of a genetic polymorphism of IL1RN with risk of acute pancreatitis in a Korean ethnic group

  • Park, Jin Woo;Choi, Ja Sung;Han, Ki Joon;Lee, Sang Heun;Kim, Eui Joo;Cho, Jae Hee
    • The Korean journal of internal medicine
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    • v.33 no.6
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    • pp.1103-1110
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    • 2018
  • Background/Aims: Several epidemiological studies have validated the association of interleukin gene polymorphisms with acute pancreatitis (AP) in different populations. However, there have been few studies in Asian ethnic groups. We aimed to investigate the relationships between inflammatory cytokine polymorphisms and AP as pilot research in a Korean ethnic group. Methods: Patients who had been diagnosed with AP were prospectively enrolled. DNA was extracted from whole blood, and DNA sequencing was subsequently performed. Single-nucleotide polymorphisms (SNPs) of the interleukin $1{\beta}$ (IL1B), interleukin 1 receptor antagonist (IL1RN), and tumor necrosis factor ${\alpha}$ (TNFA) genes of patients with AP were compared to those of normal controls. Results: Between January 2011 and January 2013, a total of 65 subjects were enrolled (40 patients with AP vs. 25 healthy controls). One intronic SNP (IL1RN -1129T>C, rs4251961) was significantly associated with the risk of AP (odds ratio, 0.304; 95% confidence interval, 0.095 to 0.967; p = 0.043). However, in our study, AP was not found to be associated with polymorphisms in the promoter regions of inflammatory cytokine genes, including IL1B (-118C>T, c47+242C>T, +3954C/T, and -598T>C) and TNFA (-1211T>C, -1043C>A, -1037C>T, -488G>A, and -418G>A). Conclusions: IL1RN -1129T>C (rs4251961) genotypes might be associated with a significant increase of AP risk in a Korean ethnic group.

Effects of Provitamin D on Skin Pigmentation and Immunity (프로 비타민 D 의 피부색 조절 및 면역 효능)

  • Hyunjung Choi;Daejin Min;Eun-Jeong Choi;Seung-Han Park;Hyoung-June Kim;Won-Seok Park
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.50 no.2
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    • pp.153-161
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    • 2024
  • Vitamin D is a fat-soluble vitamin that is mainly produced in the skin by UV rays. Along with melatonin, it is a representative chronobiotic substance, and the skin plays an important role in distinguishing between day and night. However, vitamin D cannot be used directly in cosmetics because it is a vitamin that acts as a coenzyme and plays a hormonal role in regulating the expression of various types of genes. Therefore, it was to investigate the skin efficacy of provitamin D (7-dehydrocholesterol), a vitamin D precursor that can be used in cosmetics. Our findings reveal that pro vitamin D can effectively inhibit the expression of tyrosinase, the melanin-producing enzyme, thereby attenuating melanin synthesis. This skin tone regulatory effect has been corroborated in vitro using artificial skin models. Additionally, pro vitamin D demonstrated anti-inflammatory properties by suppressing the expression of TNFa and, upon conversion to vitamin D through UV exposure, it was observed to induce the production of the antimicrobial peptide CAMP (LL-37). The inhibitory effect of pro vitamin D on melanin production appears to be a result of it reducing the UV absorption capacity of melanin, thereby inducing the conversion of pro D to vitamin D. Utilizing pro vitamin D in cosmetic formulations could not only modulate skin tone and enhance skin immunity but also expect to contribute to other cutaneous benefits as anti-aging and barrier function improvement with everyday UV exposure. This multifaceted efficacy positions pro vitamin D as a promising ingredient in advancing the formulation of skin care products.

Effects of Pueraria lobata on Body Weight and Gene Expression in Obese Rats Muscle with Estrogen Deficiency (갈근 추출물이 난소 적출로 비만이 유발된 Rat의 체중 변화와 유전자 발현에 미치는 영향)

  • Shin, Hee-Jong;Yoo, Jeong-Eun;Jung, Eun-Hye;Yoo, Dong-Youl
    • The Journal of Korean Obstetrics and Gynecology
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    • v.25 no.3
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    • pp.71-84
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    • 2012
  • Objectives: GG is the EtOH fraction of extract of Pueraria lobata. In this study, we aimed to elucidate a possibility that GG reduce obesity and obesity-derived complications such as cardiovascular and metabolic disease. Methods: The effects of GG on the estrogen-deficient obese rats and the level of gene expression in muscle of rats were investigated. Results: GG decreased body weight in obese rats with estrogen deficiency. GG increased leptin gene expression in obese rats with estrogen deficiency. GG decreased TNFa gene expression in obese rats with estrogen deficiency. And GG increased PPAR-gamma, PGC-1a, Prdx6, FDFT1, and ACC gene expression of those in obese rats. Conclusions: We conclude GG might reduce body weight and regulate gene expression of muscle in obese rats.

Keumsa Linteusan Suppresses Invasion of Cancer Cells through the Inhibition of Cellular Adhesion and MMP-9 Expression

  • Kim, Won-Jung;Hong, Sung-Chang;Do, Eun-Ju;Suk, Kyung-Ho;Yun, lk-Jin;Lee, Won-Ha
    • Animal cells and systems
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    • v.13 no.2
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    • pp.113-118
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    • 2009
  • Extracts derived from various medical mushrooms have been reported to have antitumor and immuno-modulatory properties. In order to investigate the antitumor activity of keumsa Linteusan, the water extract of Phellinus Iimteus, HT1080 cells, a human fibrosarcoma cell line, were treated with it and changes in cellular migration potential was tested in vitro. At a concentration range below 1,000 $\mu$g/mL, Linteusan blocked, in a dose dependent manner, the migration of cells through Matrigel as well as Boyden chamber without affecting the viability of the cells. Prolonged treatment of HT1080 cells with Linteusan suppressed TNFa induced production of matrix metalloproteinase (MMP)-9 as well as basal level expression of MMP-2. Linteusan also affected the adhesion of the cells to fibronectin-coated surfaces. The effect of Linteusan on cell signaling pathways was also tested. Linteusan specifically affected TNF-$\alpha$ induced phosphorylation of AKT in a dose-dependent manner, while phosphorylation levels of ERK remained unaffected. These data indicate that Linteusan blocks the migration of HT1080 cells by affecting various processes associated with cell migration such as the expression of matrix degradingenzymes,cell adhesion, and AKT-medicated cellular signaling pathways.

Effect of ion Pairing on the Cellular Transport of Antisense Oligonucleotide

  • Song, Kyung;Kim, Kyoung-Mi;Kim, Jae-Baek;Ko, Geon-Il;Sohn, Dong-Hwan
    • Archives of Pharmacal Research
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    • v.20 no.5
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    • pp.438-442
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    • 1997
  • Antisense oligonucleotide represents an interesting tool for selective inhibition of gene expression. However, their low efficiency of introduction within intact cells remains to be overcome. Antisense-$TGF{\beta}$ (25 mer) and antisense-$TGF{\beta}$ (18 mer) were used to study the cellular transport and biological function of antisense oligonucleotide in vitro. Since TGF and TNF play on important role in regulating the nitric oxide production from macrophages, the action of the above antisense oligonucleotides was easily monitored by the determination of nitrite. Poly-L-lysine, benzalkonium chloride and tetraphenylphosphonium chloride were used as polycations, which neutralize the negative charge of antisense oligonucleotide. The production of nitric oxide mediated by .gamma.-IFN in mouse peritoneal macrophage was increased by antisense-TGF.betha. in a dose-dependent manner. Antisense-$TGF{\beta}$ reduced the nitric oxide release from activated RAW 264.7 cells. Significant enhancement in the nitric oxide production was investigated by the cotreatment of poly-L-lysine with antisense-$TGF{\beta}$On the meanwhile, inhibition effect of antisense-$TGF{\beta}$ is not changed by the addition of poly-L-lysine. These results demonstrate that control of expression of $TGF{\beta}$ and TNF.alpha. gene is achieved using antisense technology and the cellular uptake of antisense oligonucleotide could be enhanced by ion-pairing.

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Ursodeoxycholic acid decreases age-related adiposity and inflammation in mice

  • Oh, Ah-Reum;Bae, Jin-Sik;Lee, Junghoon;Shin, Eunji;Oh, Byung-Chul;Park, Sang-Chul;Cha, Ji-Young
    • BMB Reports
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    • v.49 no.2
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    • pp.105-110
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    • 2016
  • Ursodeoxycholic acid (UDCA), a natural, hydrophilic nontoxic bile acid, is clinically effective for treating cholestatic and chronic liver diseases. We investigated the chronic effects of UDCA on age-related lipid homeostasis and underlying molecular mechanisms. Twenty-week-old C57BL/6 male and female mice were fed a diet with or without 0.3% UDCA supplementation for 25 weeks. UDCA significantly reduced weight gain, adiposity, hepatic triglyceride, and hepatic cholesterol without incidental hepatic injury. UDCA-mediated hepatic triglyceride reduction was associated with downregulated hepatic expression of peroxisome proliferator-activated receptor-γ, and of other genes involved in lipogenesis (Chrebp, Acaca, Fasn, Scd1, and Me1) and fatty acid uptake (Ldlr, Cd36). The inflammatory cytokines Tnfa, Ccl2, and Il6 were significantly decreased in liver and/or white adipose tissues of UDCA-fed mice. These data suggest that UDCA exerts beneficial effects on age-related metabolic disorders by lowering the hepatic lipid accumulation, while concurrently reducing hepatocyte and adipocyte susceptibility to inflammatory stimuli.

Effect of Lectin Isolated from Serrognathus platymelus castanicolor Larvae on the Various Cytokine Expressions (넓적사슴벌레(Serrognathus platymelus castanicolor) 유충으로부터 분리한 렉틴의 사이토카인 발현)

  • Jo, Su-Hyun;Kim, Se-Jin;Chung, See-Ryun;Jeune, Kyung-Hee
    • Korean Journal of Pharmacognosy
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    • v.37 no.4 s.147
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    • pp.221-228
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    • 2006
  • A lectin was purified from Serrognathus platymelus castanicolor larvae and named as SPL. The purification was carried out by ion-exchange chromatography on DEAE Sephadex A-50 and gel filtration chromatography on Sephadex G-200. The purity of the protein was verified by polyacrylamide gel electrophoresis and the purified lectin agglutinated erythrocytes of rabbit and human A, B, O, AB. SPL was tested it's ability to enhance the expressions of cytokines, $IL-1\alpha$, IL-2, IL-6, $TNF\alpha$ and $IFN\gamma$ by human peripheral blood mononuclear cells (PBMC) obtained from healthy donors. mRNA analyses were performed by RT-PCR at the moment of 1, 4, 8, 24, 48, 72 and 96 h after stimulation of PBMC with purified SPL. The patterns of IL-2 band were slightly expressed from 24 h and the strongest band was appeared at 96 h. The expressions of $IL-1\alpha$ and IL-6 mRNA were strong from 1 to 8 h and those of $TNF\alpha$ were from 48 to 96 h. The mRNA encoding $IFN\gamma$ were not detected. The addition of SPL for macrophage cultures induced production of nitric oxide (NO) by cells in a dose-dependent manner. NO release was partially inhibited by $TNF\alpha$ antibodies. These results suggest that SPL has the ability to enhance cytokine expressions in PBMC and to induce the NO release by TNFa in macrophage cultures from PBMC cultures.