• Title/Summary/Keyword: Tumor Necrosis Factor

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Molecules of the Tumor Necrosis Factor (TNF) Receptor and Ligand Superfamilies: Endless Stories

  • Kwon, Byung-Suk;Kwon, Byoung-Se
    • BMB Reports
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    • v.32 no.5
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    • pp.419-428
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    • 1999
  • Tumor necrosis factor (TNF) receptor members have unique structures composed of 2-4 cysteine - rich pseudorepeats in the extracellular domain. On ligation by trimeric ligand molecules, oligomerization of three receptor molecules occurs, which in turn activates the receptor and recruits intracellular signaling molecules to the cytoplasmic tail to initiate biological events. Recently, the numbers of tumor necrosis factor receptor and ligand family members have been rapidly expanding. Functional characterization of the new members has indicated redundant roles with other known members as well as provided insights into novel functions. In particular, identification of soluble decoy receptors which have the ability to bind multiple ligands highlights a complex control mechanism of immune responses by these molecules. Studies of the new members have also revealed that the TNF receptor and ligand family members play an important role in other than the immune system.

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Anti-Tumor Necrosis Factor Therapy in Intestinal Behçet's Disease

  • Park, Jihye;Cheon, Jae Hee
    • Gut and Liver
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    • v.12 no.6
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    • pp.623-632
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    • 2018
  • Intestinal Behçet's disease is a rare, immune-mediated chronic intestinal inflammatory disease; therefore, clinical trials to optimize the management and treatment of patients are scarce. Moreover, intestinal Behçet's disease is difficult to treat and often requires surgery because of the failure of conventional medical treatment. Administration of anti-tumor necrosis factor-${\alpha}$, a potential therapeutic strategy, is currently under active clinical investigation, and evidence of its effectiveness for both intestinal Behçet's disease and inflammatory bowel diseases has been accumulating. Here, we review updated data on current experiences and outcomes after the administration of anti-tumor necrosis factor-${\alpha}$ for the treatment of intestinal Behçet's disease. In addition to infliximab and adalimumab, which are the most commonly used agents, we describe agents such as golimumab, etanercept, and certolizumab pegol, which have recently been shown to be effective in refractory intestinal Behçet's disease. This review also discusses safety issues associated with anti-tumor necrosis factor-${\alpha}$, including vulnerability to infections and malignancy.

Expression of Tumor Necrosis Factor (TNF)-z${\alpha}$ from Cells Undergoing Death by FADD

  • Kim, Koanhoi
    • Journal of Life Science
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    • v.12 no.2
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    • pp.57-60
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    • 2002
  • Apoptosis of vascular smooth muscle cell is observed in the vascular diseases such as atherosclerosis and restenosis. The death of vascular smooth muscle cells can be induced by cytokines and activation of Fas-pathways. It is widely accepted that apoptosis occurs without inflammation. There are, however, reports that apoptosis is not silent. Vascular smooth muscle cells dying by Fas-pathway secreted inflammatory cytokines including monocyte chemoattractant protein-1. This study have investigated whether apoptosis is associated with potent inflammatory cytokine tumor tumor necrosis factor (TNF)-${\alpha}$. The cells which undergo apoptosis by expressing FADD in the absence of tetracycline expressed and secreted TNF-${\alpha}$. When the level of TNF-${\alpha}$ transcript was investigated, dying smooth muscle cells exhibited transcriptional activation of TNF-${\alpha}$. The data indicate that dying vascular smooth muscle cells contribute to inflammation by expressing inflammatory cytokines. The present study suggests that apoptosis could not be silent in certain pathological situations.

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The Lack of a Direct Effect of Tumor Necrosis Factor-Alpha on Sperm Motility (Tumor Necrosis Factor-Alpha가 정자운동성에 미치는 직접 영향의 부족)

  • Song, Eun-Seop;Lim, Young-Ku;Song, Yun-Seob
    • Clinical and Experimental Reproductive Medicine
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    • v.26 no.1
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    • pp.97-101
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    • 1999
  • Male genital tract inflammatory conditions may be associated with unexplained infertility. The presence of cytokine such as tumor necrosis factor-alpha (TNF-${\alpha}$) was reported in the semen of infertile men. However, the effect of these cytokines on human sperm function is still unclear. The purpose of this study was to investigate the in-vitro effects of TNF-alpha on human sperm motility with computer assisted sperm analysis. Washed sperm from 16 normal men were incubated without and with TNF-${\alpha}$ (0.1, 10, 1000 ng/ml). The changes of parameters of sperm motility were recorded at different time intervals (0, 5, 24 hour). There was no significant change of parameters of sperm motility in the incubation with TNF-${\alpha}$. It is suggested that TNF-${\alpha}$ alone does not interfere with the sperm motility and more studies are needed.

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The Effect of Tumor Necrosis Factor (TNF) on Gene Expression of Surfactant Protein A, B, and C (Tumor Necrosis Factor가 Surfactant Protein A, B, C의 유전자 발현에 미치는 영향에 관한 실험적 연구)

  • Choi, Jin-Won;Sohn, Jang-Won;Yang, Seok-Chul;Yoon, Ho-Joo;Shin, Dong-Ho;Park, Sung-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.4
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    • pp.513-521
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    • 2000
  • Background : TNF may play an important role(central mediator) in the development of an acute respiratory distress syndrome. Since TNF induced lung injury in the acute respiratory distress syndrome and abnormalities in surfactant function have been described in acute respiratory distress syndrome, the authors investigated the effects of TNF on the regulation of surfactant protein A, B and C mRNA accumulation. Methods : The effects of TNF on gene expression of surfactant protein A, B, and C were analyzed using filter hybridization, 12 and 24 hours after intravenous injection of TNF in rats. Results : 1. The accumulation of SP-A mRNA in the TNF treated group (12 and 24 hours after TNF injection) was significantly decreased by 22.9% and 27.4%, respectively, compared to the control group (P<.025, P<.025). 2. The accumulation of SP-B mRNA in 24 hours after TNF treated group was significantly decreased by 20.5% compared to that of the control group(P<.01). 3. The accumulation of SP-C mRNA in 12 hours after TNF treated group was significantly decreased by 31% the compared to that of the control group(P<.01). Conclusions : These findings indicate the marked inhibitory effects of tumor necrosis factor on surfactant proteins expression in vivo. This finding. in turn, supports the idea of inhibitory effects of tumor necrosis factor on surfactant proteins expression as it relates to pathogenesis of acute respiratory distress syndrome.

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Depilatory creams increase the number of hair follicles, and dermal fibroblasts expressing interleukin-6, tumor necrosis factor-α, and tumor necrosis factor-β in mouse skin

  • Tsai, Pi-Fen;Chou, Fen-Pi;Yu, Ting-Shuan;Lee, Huei-Jane;Chiu, Chun-Tang
    • The Korean Journal of Physiology and Pharmacology
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    • v.25 no.6
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    • pp.497-506
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    • 2021
  • Besides using for hair removal, depilatory agents have been considered to be used as a penetration enhancer for transepidermal drug delivery. To examine the effect in hair follicles (HFs), two commercially available depilatory creams were tested on the dorsal skin of mice to monitor the effect deep into the skin structure. Fifteen male BALB/c mice were used in this study. Depilatory creams were applied to the dorsal skin of the same animal using shaved and untouched treatments as controls to minimize individual differences. Skin samples were collected at three days, one week and two weeks (n = 5 for each) after the treatment, and subjected for hematoxylin-eosin staining, and immunohistochemical analysis for proinflammatory cytokines. The morphological examination showed an increase in the thickness of epidermal layer of the depilatory cream-treated skin at early time points and in the subcutis at two weeks. Depilatory cream promoted entry of anagen phase and increased the number of hair follicles in the subcutis at one and two weeks. Immunohistochemistry showed elevated percentages of dermal fibroblasts expressing interleukin-6, tumor necrosis factor-α, and tumor necrosis factor-β. Shaving process increased the thickness of epidermis and dermis as depilatory creams did, but did neither induce the expression of proinflammatory cytokines in the dermal fibroblasts nor the number of HFs. The results suggested that the commercially available depilatory creams caused a transient minor inflammatory response of the skin and increased the levels of cytokines that might subsequently affect hair growth.

Development of human tumor necrosis factor-α muteins with improved therapeutic potential

  • Jang, Seung-Hwan;Kim, Hyo-Jin;Cho, Kwang-Hwi;Shin, Hang-Cheol
    • BMB Reports
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    • v.42 no.5
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    • pp.260-264
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    • 2009
  • Tumor necrosis factor-$\alpha$ (TNF-$\alpha$) exhibits cytotoxicity towards various tumor cells in vitro and induces apoptotic necrosis in transplanted tumors in vivo. It also shows severe toxicity when used systemically for the treatment of cancer patients, hampering the development of TNF-$\alpha$ as a potential anticancer drug. In order to understand the structure-function relation of TNF-$\alpha$ with respect to receptor binding, we selected four regions on the bottom of the TNF-$\alpha$ trimer that are in close contact with the receptor and carried out mutagenesis studies and computational modeling. From the study, various TNF-$\alpha$ muteins with a high therapeutic index were identified. These results will provide a structural basis for the design of highly potent TNF-$\alpha$ for therapeutic purposes. By conjugating TNF-$\alpha$ muteins with a high therapeutic index to a fusion partner, which targets a marker of angiogenesis, it could be possible to develop TNF-$\alpha$ based anticancer drugs.

Different level of tumor necrosis factor-α expression after administration of silk sericin fraction in RAW264.7 cells

  • Kim, Dae-Won;Jo, You-Young;Kweon, HaeYong;Kim, Seong-Gon
    • International Journal of Industrial Entomology and Biomaterials
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    • v.41 no.1
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    • pp.1-5
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    • 2020
  • Tumor necrosis factor-α (TNFα) is a representative marker for inflammation. Silk sericin is known as mild TNFα inducer. The purpose of this study was to compare the level of TNFα among different fractions of silk sericin. Silk sericin was extracted from cocoon and separated it by molecular weight. Each fraction was applied to RAW264.7 cells. The level of TNFα was evaluated by western blot and ELISA assay. In results, the level of TNFα was increased as time-dependent manner. Higher molecular weight fraction of sericin induced higher amount of TNFα than lower molecular weight fraction. In conclusion, different molecular weight fraction of sericin induced TNFα differently.