• 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.

• 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.

• 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.

• 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.

• 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.

• 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.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.

• Toxicological Research
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• v.13 no.3
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• pp.203-208
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• 1997

The antigenic potential of M3S tumor necrosis factor-$\alpha$(M3S TNF), which is a mutated form of TNF(TNF mutein) designed to reduce adverse effects of wild type human TNF, was investigated in the present study. The antigenicity of M3S TNF was examined by conducting active systemic anaphylaxis (ASA) test in guinea pigs, heterologous(mouse-rat) passive cutaneous anaphylaxis(PCA) test and passive hemagglutination(PHA) test. The experimental animals were divided into low, medium, high and the highest dose groups and the groups with or without immunoadjuvant, sensitized according to the appropriate schedule and challenged. In ASA test, when challenged with 120 $\mu\textrm{g}$ /animal, moderate to severe positive anaphylactic responses were observed in groups sensitized with 12 $\mu\textrm{g}$ /animal, 120 $\mu\textrm{g}$ /animal and 120 $\mu\textrm{g}$ /animal+Freund's complete adjuvant. In PCA test, positive responses were observed in the group sensitized with the highest dose emulsified with an alum(12 $\mu\textrm{g}$ /animal+alum). In PHA test, positive responses were observed in the group sensitized with 3 $\mu\textrm{g}$ /animal emulsified with an alum. All the other groups in each experiment showed negative responses. Based on these results, M3S TNF is considered to have some antigenic potential.

• 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.

• Proceedings of the PSK Conference
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• 2002.10a
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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)