• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8533-8539
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• 2016

Background: B-cell chronic lymphocytic leukemia B (B-CLL), the most common type of leukemia, may be caused by apoptosis deficiency in the body. Adipose tissue-derived mesenchymal stem cells (AD-MSCs) as providers of pro-apoptotic molecules such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), can be considered as an effective anti-cancer therapy candidate. Therefore, in this study we assessed the role of tumor necrosis factor-producing mesenchymal stem cells oin apoptosis of B-CLL cells resistant to fludarabine-based chemotherapy. Materials and Methods: In this study, after isolation and culture of AD-MSCs, a lentiviral LeGO-iG2-TRAIL-GFP vector containing a gene producing the ligand pro-apoptotic with plasmid PsPAX2 and PMDG2 virus were transfected into cell-lines to generate T293HEK. Then, T293HEK cell supernatant containing the virus produced after 48 and 72 hours was collected, and these viruses were transduced to reprogram AD-MSCs. Apoptosis rates were separately studied in four groups: group 1, AD-MSCs-TRAIL; group 2, AD-MSCs-GFP; group 3, AD-MSCs; and group 4, CLL. Results: Observed apoptosis rates were: group 1, $42{\pm}1.04%$; group 2, $21{\pm}0.57%$; group 3, $19{\pm}2.6%$; and group 4, % $0.01{\pm}0.01$. The highest rate of apoptosis thus occurred ingroup 1 (transduced TRAIL encoding vector). In this group, the average medium-soluble TRAIL was 72.7pg/m and flow cytometry analysis showed a pro-apoptosis rate of $63{\pm}1.6%$, which was again higher than in other groups. Conclusions: In this study we have shown that tumor necrosis factor (TNF) secreted by AD-MSCs may play an effective role in inducing B-CLL cell apoptosis.

• BMB Reports
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• 제48권10호
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• pp.559-564
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• 2015

We investigated the effects of mangiferin on the expression and activity of metalloproteinase (MMP)-9 and the invasion of tumor necrosis factor (TNF)-$\alpha$-stimulated human LNCaP prostate carcinoma cells. Reverse-transcription polymerase chain reaction (RT-PCR) and western blot analysis showed that mangiferin significantly reversed TNF-$\alpha$-induced mRNA and protein expression of MMP-9 expression. Zymography data confirmed that stimulation of cells with TNF-$\alpha$ significantly increased MMP-9 activity. However, mangiferin substantially reduced the TNF-$\alpha$-induced activity of MMP-9. Additionally, a matrigel invasion assay showed that mangiferin significantly reduced TNF-$\alpha$-induced invasion of LNCaP cells. Compared to untreated controls, TNF-$\alpha$-stimulated LNCaP cells showed a significant increase in nuclear factor-${\kappa}B$ (NF-${\kappa}B$) luciferase activity. However, mangiferin treatment markedly decreased TNF-$\alpha$-induced NF-${\kappa}B$ luciferase activity. Furthermore, mangiferin suppressed nuclear translocation of the NF-${\kappa}B$ subunits p65 and p50. Collectively, our results indicate that mangiferin is a potential anti-invasive agent that acts by suppressing NF-${\kappa}B$-mediated MMP-9 expression.

• 한국동물생명공학회지
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• 제36권4호
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• pp.307-313
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• 2021

Traf4 (Tumor necrosis factor Receptor Associated Factor 4) is a member of the tumor necrosis factor receptor (TNFR) - associated factors (TRAFs) family. TRAF4 is overexpressed in tumor cells such as breast cancer and associated with cytoskeleton and membrane fraction. Interestingly, TRAF4 was localized with tight junctions (TJs) proteins including OCLN and TJP1 in mammary epithelial cells. However, the expression patterns and biological function of Traf4 were not examined in preimplantation mouse embryos although Traf4-deficient mouse showed embryonic lethality or various dramatic malformation. In this study, we examined the temporal and spatial expression patterns of mouse Traf4 during preimplantation development by qRT-PCR and immunostaining, and its biological function by using siRNA injection. We found upregulation of Traf4 from the 8-cell stage onwards and apical region of cell - cell contact sites at morula and blastocyst embryos. Moreover, Traf4 knockdown led to defective TJs without alteration of genes associated with TJ assembly but elevated p21 expression at the KD morula. Taken together, Traf4 is required for TJs assembly and cell proliferation during morula to blastocyst transition.

• Pediatric Infection and Vaccine
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• 제21권3호
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• pp.225-230
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• 2014

최근 가와사키병에서 tumor necrosis factor-alpha(TNF-alpha) blocker인 infliximab 단일 정주 요법이 불응성 가와사키병 환자들에게 유용한 치료제로 여겨지고 있다. 장기적인 TNF-alpha blocker 사용이 기회감염의 위험을 증가시킬 수 있지만, 가와사키병 환자들에게 infliximab 사용이 심각한 부작용을 초래하지 않으며 안전하게 사용된 증례들이 보고된 바 있다. 불응성 가와사키병을 앓고 있는 5개월 된 영아에서 infliximab (5 mg/kg) 단일 정주 요법을 사용하였고 가와사키 증상이 호전되었으나 infliximab 치료 후 Acinetobacter lwoffii에 의한 패혈증이 발생하였다. 그래서 저자들은 불응성 가와사키병을 앓은 영아에서 infliximab 치료 후 발생한 패혈증의 첫 사례를 보고하며 infliximab 치료 선택에 있어 기회 감염의 위험성에 대해 고려할 것을 당부하는 바이다.

• Biotechnology and Bioprocess Engineering:BBE
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• 제9권4호
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• pp.292-296
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• 2004

The recombinant soluble human tumor necrosis factor-alpha (hTNF-$\alpha$) was expressed in a yeast Saccharomyces cerevisiae and its cytotoxicity was evaluated. A cDNA encoding hTNF-$\alpha$ was placed under the control of two different promoters: a glyceraldehyde-3-phosphate dehydrogenase (GPD) promoter and a yeast hybrid ADH2-GPD promoter, consisting of alcohol dehydrogenase II (ADH2) and the GPD promoter. A Northern blot analysis revealed that, although variation in the expression level of hTNF-$\alpha$ existed among transformants, the higher expression was obtained with the GPD promoter. Expressed hTNF-$\alpha$ protein (rhTNF-$\alpha$) was successfully secreted into the culture medium, producing 2.5 mg per liter of culture filtrate, with no changes in cell growth. The bioassay for observing the cytotoxicity to the murine L929 fibroblast cell line, with serial dilution of rhTNF-$\alpha$, indicated that the secreted rhTNF-$\alpha$ was bioactive and its dose-response was improved eight to ten times over that of the E. coli-derived rhTNF-$\alpha$.

• Natural Product Sciences
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• 제5권2호
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• pp.70-74
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• 1999

In the course of a search for tumor necrosis factor $(TNF)-{\alpha}$ inhibitory compounds from medicinal plants, we identified neolignans, honokiol and magnolol, from the alcoholic extract of Magnolia offcinalis as active inhibitory principles. These compounds dose-dependently inhibited $TNF-{\alpha}$ production without displaying cytotoxicity and their inhibitory activities measured by $IC_{50}$ values were 53.7 and $61.4\;{\mu}M$, respectively.

• 동의생리병리학회지
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• 제16권5호
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• pp.1020-1024
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• 2002

The purpose of this research was to investigate the effects of Kamidaebo-tang water extract (KDT) on murine peritoneal macrophages. KDT (50 or 250 mg/kg) was administerd p.o. once a day for 7 days to mice. KDT increased the production of tumor necrosis factor-α and nitric oxide from murine peritoneal macrophages, but decreased the production of interleukin-1β. Also, KDT enhanced the production of lucigenin chemiluminescence from peritoneal macrophages. These results suggest that KDT enhances the non-specific immune response via increase of tumor necrosis factor-α and nitric oxide and phagocytic activity from peritoneal macrophages.

• Advances in Traditional Medicine
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• 제10권1호
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• pp.37-43
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• 2010

Palmitic acid (PA) is one of free fatty acids, which is found from Gaultheria itoana Hayata and Sarcopyramis nepalensis. Although PA has a variety of pharmacological effects including mediates hypothalamic insulin resistance, induces IP-10 expression, and promote apoptotic activities, the anti-inflammatory mechanism of PA in mouse peritoneal macrophages remains unclear. In this study, we showed that PA exerted an anti-inflammatory action through suppression the production of tumor necrosis factor-$\alpha$, interleukin-6, cyclooxygenases-2 and nitric oxide in lipopolysaccaride-stimulated mouse peritoneal macrophages. Our study suggests an important molecular mechanism of PA, which might explain its beneficial effect in the regulation of inflammatory reactions.

• Advances in Traditional Medicine
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• 제2권2호
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• pp.106-112
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• 2002

The effect of aqueous extract of Magnoliae Cortex (Magnoliaceae) (MCAE) on the immediate-type allergic reaction was investigated. MCAE inhibited compound 48/80 induced systemic anaphylactic reaction in rats. MCAE (0.1 and 1 g/kg) also significantly inhibited local immunoglobulin E (lgE)-mediated passive cutaneous anaphylactic (PCA) reaction. MCAE (0.001 to 1 mg/ml) dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-dinitrophenyl (DNP) 1gE. Moreover, MCAE (0.01 to 1 mg/ml) had a significant inhibitory effect on anti-DNP IgE-mediated tumor necrosis $factor-{\alpha}$ $(TNF-{\alpha})$ production. These results indicate that MCAE inhibits immediate-type allergic reaction in vivo and in vitro.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제15권1호
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• pp.13-18
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• 2012

The pathogenesis of inflammatory bowel diseases is not very well understood; it is currently thought to be caused by the interaction between genetic factors, environmental factors, intestinal microbes, and immune factors. Biological agents such as anti-tumor necrosis factor (anti-TNF) are widely being used as therapeutic agents. Infliximab, a chimeric monoclonal IgG1 antibody against tumor necrosis factor, has been demonstrated to have an effect in the induction and maintenance of remission in Crohn's disease in children. The effects of biological agents, typified by anti-TNFs, in inflammatory bowel disease in children; the recent concern on the administration of biological agents in combination with immunomodulators; and 'Top-down' therapy are some of the topics covered in this review.