• Gut and Liver
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• 제12권6호
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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.

• BMB Reports
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• 제32권5호
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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.

• Tuberculosis and Respiratory Diseases
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• 제48권4호
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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.

• BMB Reports
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• 제42권5호
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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.

• Clinical and Experimental Reproductive Medicine
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• 제26권1호
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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.

• The Korean Journal of Physiology and Pharmacology
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• 제25권6호
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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.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.293.2-293.2
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• 2002

Bisphenol A ［BPA. 2.2-bis(4-hydroxyphenyl)propane］ is reported to have estrogenic activity: however. its influence on cytokine production or immune system function remains unclear. In this study. we investigated the effects of BPA on the production of nitric oxide (NO) and tumor necrosis factor-a (TNF-a), and on the level of inducible nitric oxide synthase (iNOS) and TNF-a gene expression in mouse macrophages. BPA alone did not affect NO or TNF-a production. (omitted)

• Toxicological Research
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• 제11권2호
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• pp.169-173
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• 1995

The effects of tumor necrosis factor alpha $(TNF-{\alpha})$ on growth and tubular formation of bovine aortic endothelial cells were examined using an in vitro angiogenesis model system. The growth of endothelial cells was enhanced in a dose-dependent manner when the cells were cultured with $TNF-{\alpha}$ for 3 days, but $TNF-{\alpha}$, at the concentration of 1 nM or higher, produced a growth inhibition of endothelial cells when the cells were cultured for 8 days. The endothelial cells incubated with $TNF-{\alpha}$ for 48-h exhibited a typical morphologic change. Then, they showed a fibroblastoid organization of overlapping, elongated, and spindle-shaped cells. $TNF-{\alpha}$, at the concentration of O. 1 nM or higher, inhibited the tubular formation of vascular endothelial cells in an in vitro anglogenesis model using a 3-dimensional culture system.

• Archives of Pharmacal Research
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• 제22권4호
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• pp.348-353
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• 1999

Possible antiinflammatory effect of eudesmin were examined by assessing the effects on tumor necrosis factor (TNF)-$\alpha$ production and lymphocyte proliferation as well as cytotoxicity against murine and human macrophages. the compound significantly inhibited TNF-$\alpha$, production by lipopolysaccaride (LPS)-stimulated murine macrophage RAW264.7 without displaying cytotoxicity suggesting that eudesmin may inhibit TNF-$\alpha$ production without any interference of normal cell function. It also significantly attenuated T cell proliferation stimulated by concanavalin A (Con A) in a dose-dependent manner.

• 동의생리병리학회지
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• 제35권1호
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• pp.15-21
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• 2021

Donggwaja (Benincasae Semen), the seed of Benincasa hispida (Thunb.) Cogn., has been used in Korean traditional medicine to control the body heat and water retention caused by various diseases. Both the symptoms targeted by the herbal medicine in clinic and studies with disease mouse models support the potential anti-inflammatory effect of Donggwaja. However, it is less understood how Donggwaja exerts its possible anti-inflammatory effect. Here, we present evidence that Donggwaja suppresses macrophage inflammatory reactions via expressing tumor necrosis factor a-induced protein 3 (TNFAIP3 or A20) and suppressing NF-kB activity. The ethanol extract of Donggwaja (EED) showed no toxicity when added to RAW 264.7 cells less than 100mg/ml. When treating the cells for 16 h, EED significantly suppressed the nuclear localization of NF-kB, suggesting that EED suppresses NF-kB activity. Concordantly, a semi-quantitative RT-PCR analysis showed that EED decreased the expression of prototypic pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-a, IL(interleukin)-6, and IL-1b. EED induced in RAW 264.7 cells the expression of A20, a ubiquitin modulator that suppresses inflammatory signaling cascades initiated from TLR4 and TNF and IL-1 receptors, while not affecting the induction of Nrf2, an anti-inflammatory factor that could suppress the effect of NF-kB. These results suggest that EED exerts its suppressive effect on inflammation, at least in part, by expressing anti-inflammatory factor A20 and suppressing pro-inflammatory factor NF-kB activity.