• Reproductive and Developmental Biology
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• v.28 no.3
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• pp.203-207
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• 2004

The transgenic mice carrying human Interleukin-10 (hIL-10) gene in conjunction with bovine (3 -casein promoter express hIL-10 in milk during lactation. In this study, stability of germ line transmission and expression of hIL-10 transgene integrated into host chromosome were monitored up to generation F8 of transgenic mice. When male mouse of generation F8 was crossbred with normal females, approximately half of offspring (50.9±5.8%) were identified as transgenic mice. Generation F9 to F15 mice also showed similar transmission rates (66.0±20.1%, 61.5±16.7%, 41.1±8.4%, 40.7±20.3%, 61.3±10.8%, 49.2±18.8% and 43.8±25.9%, respectively), implying that hIL-10 transgene can be transmitted stably up to long term generation in the transgenic mice. Expression levels of human IL-10 from milk of generation F9 to F14 mice were 3.6± 1.2 mg/ml, 4.2±0.9 mg/ml, 5.7±1.5 mg/ml, 6.3±3.5 mg/ml, 6.8±4.5 mg/ml and 6.8±3.1 mg/ml, respectively, which was showed high-level expression compared with that of generation F1 (1.6 mg/ml) mice. In conclusion, our results suggest that transgenic mice can be continuously passed their transgenes to the progeny through the breeding program with the same productivity of human IL-10 protein in their milk.

• IMMUNE NETWORK
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• v.20 no.3
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• pp.27.1-27.11
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• 2020

Although various studies on predictive markers in the use of PD-1/PD-L1 inhibitors are in progress, only PD-L1 expression levels in tumor tissues are currently used. In the present study, we investigated whether baseline serum levels of IL-6 can predict the treatment response of patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors. In our cohort of 125 NSCLC patients, the objective response rate (ORR) and disease control rate (DCR) were significantly higher in those with low IL-6 (<13.1 pg/ml) than those with high IL-6 (ORR 33.9% vs. 11.1%, p=0.003; DCR 80.6% vs. 34.9%, p<0.001). The median progression-free survival was 6.3 months (95% confidence interval [CI], 3.9-8.7) in the low IL-6 group, significantly longer than in the high IL-6 group (1.9 months, 95% CI, 1.6-2.2, p<0.001). The median overall survival in the low IL-6 group was significantly longer than in the high IL-6 group (not reached vs. 7.4 months, 95% CI, 4.8-10.0). Thus, baseline serum IL-6 levels could be a potential biomarker for predicting the efficacy and survival benefit of PD-1/PD-L1 inhibitors in NSCLC.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.213-220
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• 2023

The most common skin disease, acne, often occurs in adolescence, but it is also detected/observed in adults due to air pollution and drug abuse. One of the causative agents of acne, Cutibacterium acnes (C. acnes) plays a role in the development of skin acne by inducing inflammatory mediators. Torreya nucifera (TN) is an evergreen tree of the family Taxaceae, having well reported antioxidant, anti-proliferative, liver protection, and nerve protection properties. Improvement of these bioactive properties of natural products is one of the purposes of natural product chemistry and pharmaceuticals. We believe biorenovation could be one improvement strategy that utilizes microbial metabolism to produce unique derivatives having enhanced bioactivity. Therefore, in this study, the C. acnes-induced RAW264.7 inflammation model was used to evaluate the anti-inflammatory activity of the biorenovated Torreya nucifera product (TNB). The results showed improved viability of TNB-treated cells compared to TN-treated cells in the concentration range of 50, 100, and 200 ㎍/mL. At non-toxic concentrations, TNB inhibited the production of nitric oxide and prostaglandin E2 by suppression of inducible nitric oxide synthase and cyclooxygenase-2 protein expression. TNB also attenuated the expression of interleukin-1β, interleukin-6, interleukin-8, and tumor necrosis factor-α induced by C. acnes. Furthermore, TNB inhibited the nuclear factor-κB signaling pathway, a transcription factor known to regulate inflammatory mediators. Based on these results, this study suggests the potential of using TNB as natural material for the treatment of acnes and thus, supporting our postulation of biorenovation as an bioactivity improvement strategy.

• BMB Reports
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• v.33 no.6
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• pp.463-468
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• 2000

Anthrax lethal toxin, which consists of two separate protein, protective antigen (83 KDa) and lethal factor (85 KDa) is responsible for major symptoms and death from systemic infection of Bacillus anthracis. High concentrations of this toxin are cytolytic to macrophages, whereas sublytic concentrations of lethal toxin induce these cells to produce interleukin $1{\beta}$ ($IL-1{\beta}$). It is proposed that melatonin and dehydroepiandrosterone (DHEA) may play an important role in modifying immune dysfunction. In this study, we investigated whether or not melatonin and DHEA could prevent $IL-1{\beta}$ production that is induced by anthrax lethal toxin in mouse peritoneal macrophages. Treatment of melatonin or DHEA alone, as well as together, prevented the production of $IL-1{\beta}$ caused by anthrax lethal toxin. We found that melatonin at a concentration of $10^{-6}-10^{-7}$ M inhibits $IL-1{\beta}$ production induced by anthrax lethal toxin. As expect, treatment of DHEA at a concentration $10^{-6}-10^{-7}$ M also suppressed production of $IL-1{\beta}$ by lethal toxin stimulated macrophages. The results of these studies suggest that melatonin and DHEA, immunomodulators, may have an important role in reducing the increase of cytokine production in anthrax lethal toxin-treated macrophages.

• Parasites, Hosts and Diseases
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• v.34 no.3
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• pp.185-190
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• 1996

The TH cytokine responses of spleen cells stimulated with Con A from mice infected with Polasonimw westemcni were examined. The spleen cell culture supema- tants were assayed for TH1-specific $IFN-{\gamma}$ and TH2-specific IL-4. Cytokine responses for IL-4 peaked at three days ($410{\;}{\pm}{\;}60.9{\;}pg/ml$), persisted at a high level until the second week ($343{\;}{\pm}{\;}59.0{\;}pg/ml$), and then decreased slowly four and six weeks after infection. $IFN-{\gamma}$ production by splenocytes only increased during the first week ($151{\;}{\pm}{\;}32.3{\;}pg/ml$) and declined abruptly after the second week of infection. IFN- y production by splenocytes of infected mice was not observed during the sixth week of infection. In addition, serum IL-4 and $IFN-{\gamma}$ were measured. Serum IL-4 was not detected in substantial quantity until four to six weeks after infection. The time course of serum IL-4 was not correlated with that of IL-4 production by splenocytes. Serum $IFN-{\gamma}$ was undetectable during the entire course of infection. These results suggest that TH2 cytokine responses, rather than TH1, predominate in mice infected with P. westemcni.

• The Journal of Korean Medicine
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• v.26 no.4
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• pp.1-11
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• 2005

This study was to investigate the effect of Danchunwhangagam(DCWGG) extract on the production of proinflammatory cytokines in peripheral blood mononuclear cells (PBMCs) from Cerebral infarction(CI) patients. Methods: We examined how the inhibition rate of tumor necrosis factor (TNF)-$\alpha$, interleukin(IL)-1$\alpha$, IL-1$\beta$, IL-6, and IL-8 productions in DCWGG pretreatment PBMCs culture supernatant in the lipopolysaccaride(LPS)- or desferrioxamine(DFX)treated cells compared to unstimulated cells. Results: DCWGG inhibited the productions of TNF-$\alpha$, IL-1$\alpha$, IL-1$\beta$, IL-6, and IL-8 induced by LPS in a dose-dependent manner. Conclusions: DCWGG might have regulatory effects on LPS or DFX-induced cytokine production, which might explain its beneficial effect in the treatment of CI.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.4
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• pp.929-935
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• 2006

This study was to investigate the effect of Danchunwhangagam(DCWGG) extract on the production of proinflammatory cytokines in peripheral mononuclear cells (PBMCS) from Cerebral infarction(CI) patients. Methods: We examined that the inhibition rate of tumor necrosis factor $(TNF)-{\alpha},\;interleukin(IL)-1{\alpha},\;IL-1{\beta}$, IL-6, and IL-8 productions in DCWGG pretreatment PBMCs culture supernatant in the lipopolysaccaride(LPS)- or Oesferrioxamine(DFX)-treated cells compared to unstimulated cells. DCWGG inhibited the productions of $TNF-{\alpha},\;IL-1{\alpha},\;IL-1{\beta}$, IL-6, and IL-8 induced by LPS in a dose-dependent manner DCWGG might have regulatory effects on LPS or DFX-induced cytokine production, which might explain its beneficial effect in the treatment of CI.

• Biomedical Science Letters
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• v.23 no.3
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• pp.272-276
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• 2017

HOX genes are transcription factors that play important roles in body patterning and cell fate specification during normal development. In previous study, we found aberrant overexpression of HOXB5 in breast cancer tissues and cell lines, and demonstrated that HOXB5 is important in regulation of cell proliferation, tamoxifen resistance, and invasiveness through the epithelial-mesenchymal transition (EMT). Although the relationship between HOXB5 and phenotypic changes in MCF7 breast cancer cells has been studied, the molecular function of HOXB5 as a transcription factor remains unclear. IL-6 has been reported to be involved in not only inflammation but also cancer progression, which is characterized by the increase of growth speed and invasiveness of tumor cells. In this study, we selected Interleukin-6 (IL-6) as HOXB5 putative downstream target gene and discovered that HOXB5 transcriptionally up-regulated the expression of IL-6 in HOXB5 overexpressing MCF7 cells. The upstream region (~1.2 kb) of IL-6 promoter turned out to contain several putative HOX consensus binding sites. Chromatin immunoprecipitation assay confirmed that HOXB5 directly binds to the promoter region of IL-6 and positively regulated the expression of IL-6. These data all together, indicate that HOXB5 promotes IL-6 transcription by actively binding to the putative binding sites located in the upstream region of IL-6, which enable to increase its promoter activity in MCF7 breast cancer cells.

• Proceedings of the Korean Society of Crop Science Conference
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• 2022.10a
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• pp.312-312
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• 2022

Peanut hull as by-product has been discarded during peanut processing. However, peanut hull contains plenty of polyphenols that shows various physiological activities. The objectives of this study were to investigate anti-inflammatory and enzyme inhibitory activities of polyphenols from 'Sinpalkwang' peanut (Arachis hypogaea L.) hull. Compounds were isolated from methanol extracts of peanut hull by preparative-high performance liquid chromatography after identifying and quantifying polyphenols using Ultra performance liquid chromatography (UPLC) and UPLC-Quadrupole time-of-flight-mass spectrometry profiling. The structures of compounds were elucidated by one-dimensional [¹H, ¹³C] nuclear magnetic resonance (NMR) and two-dimensional NMR (correlated spectroscopy, heteronuclear single quantum coherence and heteronuclear multiple bond correlation). Three compounds were identified as 5,7-dihydroxy-4H-chromen-4-one (peak 2), luteolin (peak 4) and eriodictyol (peak 5). Significant differences in inflammatory mediator such as nitric oxide (NO), interleukin-6 (IL-6) and interleukin-1β (IL-lβ) in lipopolysaccharide stimulated Raw 264.7 macrophages and in enzyme (xanthine oxidase [XO] and α-glucosidase [AG]) inhibitory activities were observed between three compounds (p < 0.05). Peak 5 treated Raw 264.7 macrophages showed lower content of NO (16.4 uM), IL-6 (7.0 ng/mL), and IL-1β (60.6 pg/mL) than peak 2 (NO: 28.3 uM, IL-6: 11.3 ng/mL, IL-1β: 66.9 pg/mL) and peak 4 (NO: 24.7 uM, IL-6: 9.3 ng/mL, IL-1β: 62.6 pg/mL). Peak 5 showed higher XO inhibitory activity (84.7%) and higher AG inhibitory activity (52.4%) than peak 2 (XO inhibitory activity: 45.4%, AG inhibitory activity: 21.6%) and peak 4 (XO inhibitory activity: 37.9%, AG inhibitory activity: 37.5%) at concentration of 0.5mg/mL. This study suggests that peanut hull could be a potential source of anti-inflammatory and physiological materials while creating new use of discarded peanut hull as by-products concomitantly.

• Biomedical Science Letters
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• v.24 no.3
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• pp.168-174
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• 2018

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by abdominal pain, rectal bleeding and diarrhea. Gastrodia elata Blume (GE) has been used for the treatment of various diseases including neurodegenerative diseases and inflammatory disease. However, there has been no information on whether GE regulates intestinal inflammation. The aim of this study is to elucidate whether GE can protect against dextran sulfate sodium (DSS)-induced colitis in a mouse model. The colitis mice were induced by drinking water containing 5% DSS for 7 days. Body weight, colon length and clinical score were assessed to determine the effects on colitis. The levels of inflammatory cytokines, tumor necrosis factor $(TNF)-{\alpha}$ and interleukin (IL)-6 in colitis tissue were also measured. The results showed that mice administrated with DSS showed clinical signs including weight loss and reduced colon length. GE inhibited the DSS-induced loss of body weight and shortening of colon and increased Disease activity index score. Additionally, we observed that GE suppressed the levels of $TNF-{\alpha}$ and IL-6 in DSS-treated colon tissues. Collectively, these findings provide experimental evidence that GE might be a useful therapeutic agent for patients with UC.