• 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.

• 대한한약학회:학술대회논문집
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• 2007.11a
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• pp.145-160
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• 2007

• 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.

• 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.

• Toxicological Research
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• v.11 no.2
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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.

• 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.

• Archives of Pharmacal Research
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• v.22 no.4
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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.

• Journal of Life Science
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• v.16 no.7 s.80
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• pp.1207-1213
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• 2006

Tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$ has been implicated in skeletal diseases by promoting bone loss in inflammatory bone diseases. In the present study, we examined the effects of $TNF-{\alpha}$ on osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). $TNF-{\alpha}$ dose-dependently promoted matrix mineralization of hBMSCs with a maximal stimulation at 2ng/ml. $TNF-{\alpha}$ increased expression of alkaline phosphatase, which plays a crucial role for the matrix deposition. The $TNF-{\alpha}-stimulated$ osteoblastic differentiation was not affected by $NF_kB$ inhibitors, BAY and SN50. However, a JNK-specific inhibitor, SP600125 completely abolished the $TNF-{\alpha}-stimulated$ matrix mineralization and expression of alkaline phosphatase. These results suggest that $TNF-{\alpha}$ enhances osteoblastic differentiation of hBMSCs through JNK-dependent pathway.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.11a
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• pp.43-50
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• 2002

• BMB Reports
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• v.29 no.6
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• pp.530-534
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• 1996

Astrocyte are the major glial cell type in the central nervous system (CNS), and analogous to macrophage, mediates the number of immune responses such as production of cytokines including tumor necrosis factor alpha ($TNF-{\alpha}$) upon activation. $TNF-{\alpha}$ has been implicated in neuroimmunological disorders through killing oligodendrocytes and thus causing demyelination. It has been previously demonstrated that mitogen-activated T cells synthesized a 26 kDa precursor form of $TNF-{\alpha}$ which is bound to the surface of a membrane, and is later secreted as a 17 kDa mature version. In order to examine whether astrocytes would produce the transmembrane form of $TNF-{\alpha}$, astrocytes were stimulated with biological stimuli and the membrane form of $TNF-{\alpha}$ was analyzed by Western blot and FACS analysis. When astrocytes are stimulated with lipopolysaccharide (LPS), $IFN-{\gamma}/LPS$, or $IFN-{\gamma}/IL-1{\beta}$, they were able to express a membrane-anchored $TNF-{\alpha}$ of approximately 26 kDa protein which was immunoreactive to an $anti-TNF-{\alpha}$ antibody, whereas unstimulated astrocytes or astrocytes treated with $IFN-{\gamma}$ or $IL-1{\beta}$ alone was not. Our FACS data were also consistent with the immunoblot analysis. Our result suggests that the membrane form of $TNF-{\alpha}$ expressed by activated astrocytes may cause local damage to oligodendrocytes by direct cell-cell contact and contribute to demyelination observed in multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE).