• 혜화의학회지
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• 제16권2호
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• pp.267-280
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• 2007

Gupoongjeseuptang(GPJST) is a traditional herbal medicine used for the treatment of dermatitis. The aim of this study was to confirm whether or not GPJST has a preventive effect on development of atopic dermatitis in dinitrochlorobenzene(DNCB)-applied Nc/Nga mouse. This study was undertaken to develop a reliable mouse model demonstrating similar immunologic phenomena as human atopic dermatitis characterized with predominance of type-2 immune response. NC/Nga mouse were sensitized with $200\;{\mu\ell}$ of 1% 2,4-dinitrochlorobenzene(DNCB) (acetone : olive oil = 3 : 1 mixture) and challenged twice or three times with $150\;{\mu\ell}$ of 0.2% DNCB in a week for the following 4 weeks. GPJST was administered orally to Nc/Nga mouse for 6 weeks, which led to the remarkable suppression on the development of dermatitis, as determined by various immune factors related to pathogenesis of atopic dermatitis in splenocytes and DLN cells. In this study, GPJST selectively suppressed T ce11 (CD4+, CD3+CD69+, CD4+CD25+) activation, which may be essential for ratio of IL-4 versus INF-$\gamma$ produced in the splenic T cell culture supernatants was approximately 3-fold higher in the mouse treated with DNCB than their control mouse respectively. Immunologic studies showed down-regulated that the capacity of spleen T cells to produce IL-4, but IFN-$\gamma$ was up-regulated by means of oral intake of these GPJST. These results strongly suggest that GPJST is a promising candidate for treatment of human atopic dermatitis.

• 사상체질의학회지
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• 제13권1호
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• pp.61-69
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• 2001

사상의학적 견지에서 태음인(太陰人)의 중풍, 치매와 같은 신경계질환에 다용되고 있는 열다한소탕(熱多寒少湯)은 최근에 그 임상적 효과를 뒷받침할 다각적인 연구들이 이루어지고 있음에도 불구하고 그 정확한 약리학적 기전에 대해서는 밝혀지지 않고 있다. 본 연구에서는 인간성상세포를 이용하여 열다한소탕(熱多寒少湯)이 substance P (SP)와 lipopolysaccharide (LPS)에 의해 유도되는 다양한 세포활성물질의 분비량의 조절을 검토함으로써 열다한소탕(熱多寒少湯)의 약리기전을 면역학적 측면에서 보다 세밀하게 살펴보고자 하였다. 열다한소탕(熱多寒少湯) 수침액은 인간 뇌 성상세포로 부터 LPS와 SP의 동시자극에 의해 생성되는 세포활성물질중 interleukin (IL)-1, IL-4, IL-6 및 tumor necrosisfaccor-${\alpha}$ (TNF-${\alpha}$)의 분비를 농도의존적으로 억제했다. 그러나 interferon-${\gamma}$ (IFN-${\gamma}$) 및 IL-2의 분비 조절에는 영향을 미치지 않았다. 그리고 항 IL-$1{\beta}$ 항체에 의해 SP 유도성 TNF-${\alpha}$ 분비의 증가가 억제되기 때문에 IL-1은 TNF-${\alpha}$ 증가를 매개하는 역할을 하는 것으로 사료된다. 이상의 결과는 열다한소탕(熱多寒少湯)에 의한 급성기 중풍환자 치료 효과가 뇌 성상세포로부터 분비되는 세포활성물질의 조절과 밀접한 관련성이 있다는 것을 암시하고 있다.

• 약학회지
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• 제47권5호
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• pp.311-318
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• 2003

Eurya emarginata (Thunb.) Makino (Theaceae) is distributed in coastal areas of island. The leaves of Eurya are used in the traditional medicine of the coastal areas of jeju island with the aim of diuresis or to treat ulcers. Nevertheless, there are few reports on the biological activity and constituents of E. emarginata. In this study, we investigated the pharmacological activity of the solvent extracts of E. emarginata on the several inflammatory markers (TNF-$\alpha$, IL-1$\beta$, IL-6, NO, iNOS and COX-2). Also we examined the antioxidizing effect of the solvent extracts by determination of DPPH radical-scavenging activity. Among the solvent fractions, EtOAc and BuOH extracts showed potent radical scavenging activity (RC$_{50}$=10.9 and 12.7 respectively). The subtractions of EF 5-4-6-3-2 and BF 1 potentially inhibited the mRNA expression of pro-inflammatory cytokines (IL-1$\beta$, IL-6 and TNF-$\alpha$) at the concentration of 100 $\mu\textrm{g}$/mι. Also the fractions inhibited the mRNA expression of pro-inflammatory cytokines (IL-1$\beta$, IL-6 and TNF-$\alpha$) and protein expression of iNOS and COX-2 at the concentration of 100 $\mu\textrm{g}$/mι. And then, the inhibition of iNOS was correlated with the decrease of nitrite level. These results suggest that E. emarginata may have anti-inflammatory activity through the inhibition of pro-inflammatory cytokines, iNOS and COX-2.2.

• Molecules and Cells
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• 제38권2호
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• pp.112-121
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• 2015

Ectopic expression of $14-3-3{\zeta}$ has been found in various malignancies, including lung cancer, liver cancer, head and neck squamous cell carcinoma (HNSCC), and so on. However, the effect of $14-3-3{\zeta}$ in the regulation of interactions between tumor cells and the immune system has not been previously reported. In this study, we aimed to investigate whether and how $14-3-3{\zeta}$ is implicated in tumor inflammation modulation and immune recognition evasion. In oral squamous cell carcinoma (OSCC) cell lines and cancer tissues, we found that $14-3-3{\zeta}$ is overexpressed. In OSCC cells, $14-3-3{\zeta}$ knockdown resulted in the up-regulated expression of inflammatory cytokines. In contrast, $14-3-3{\zeta}$ introduction attenuated cytokine expression in human normal keratinocytes and fibroblasts stimulated with interferon-${\gamma}$ (IFN-${\gamma}$) and lipopolysaccharide (LPS). Furthermore, supernatants from $14-3-3{\zeta}$ knockdown OSCC cells dramatically altered the response of peritoneal macrophages, dendritic cells and tumor-specific T cells. Interestingly, Stat3 was found to directly interact with $14-3-3{\zeta}$ and its disruption relieved the inhibition induced by $14-3-3{\zeta}$ in tumor inflammation. Taken together, our studies provide evidence that $14-3-3{\zeta}$ may regulate tumor inflammation and immune response through Stat3 signaling in OSCC.

• 생약학회지
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• 제42권3호
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• pp.253-259
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• 2011

Macrophages play a vital role in the innate immune system involving defensive cytokines such as TNF (tumor necrosis factor)-${\alpha}$ and nitric oxide (NO). Therefore, we try to elucidate the anti-inflammatory activity of Chaga mushroom (Inonotus Obliquus, IO) in murine macrophages. Raw 264.7 cells and peritoneal macrophages of mice were cultured with or without LPS/LPS + IFN-${\gamma}$ in the presence of IO aqueous extracts (IOE 0.2, 2, 20, 100 ${\mu}g$/mL) for 24 hr and 48 hr, respectively. Exposure of IOE caused the decrease of NO production and increase of TNF-${\alpha}$ production in dose-dependent manner in activated peritoneal macrophage in vitro. To further investigate anti-inflammatory effects of IO ex vivo, we orally administrated capsaicin (PC, 3 mg/kg/day) and IOE (100, 200, 400 mg/kg/day) for 4 consecutive days to C57BL/6 mice (7~9 weeks old, female), then observed the NO secretion and cytokine (TNF-${\alpha}$) production of LPS/LPS + INF-${\gamma}$-stimulated peritoneal macrophages. IOE inhibits NO secretion in dose-dependent manner both ex vivo and in vitro and increases the production of TNF-${\alpha}$ in vitro. In addition, we found that IOE possessed suppressive effects of LPS-stimulated TNF-${\alpha}$, IL-$1{\beta}$, COX-2, as well as iNOS expressions in Raw 264.7 cells. These findings indicate that IOE suppress not only the LPS-induced NO overproduction of murine peritoneal macrophages, but also iNOS, COX-2, TNF-${\alpha}$, and IL-$1{\beta}$ overexpression of LPS-induced Raw 264.7 cells. Consequently, our results suggest that IO may have the anti-inflammatory effects via suppression of the inflammatory cytokines and mediators, and be useful for the treatment of inflammatory diseases.

• Journal of Microbiology and Biotechnology
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• 제29권2호
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• pp.304-310
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• 2019

Interleukin-21 is a common ${\gamma}$-chain cytokine that controls the immune responses of B cells, T cells, and natural killer cells. Targeting IL-21 to strengthen the immune system is promising for the development of vaccines as well as anti-infection and anti-tumor therapies. However, the practical application of IL-21 is limited by the high production cost. In this study, we improved IL-21 production by codon optimization and selection of appropriate signal peptide in CHO-K1 cells. Codon-optimized or non-optimized human IL-21 was stably transfected into CHO-K1 cells. IL-21 expression was 10-fold higher for codon-optimized than non-optimized IL-21. We fused five different signal peptides to codon-optimized mature IL-21 and evaluated their effect on IL-21 production. The best result (a 3-fold increase) was obtained using a signal peptide derived from human azurocidin. Furthermore, codon-optimized IL-21 containing the azurocidin signal peptide promoted $IFN-{\gamma}$ secretion and STAT3 phosphorylation in NK-92 cells similar to codon-optimized IL-21 containing original signal peptide. Collectively, these results indicate that codon optimization and azurocidin signal peptides provide an efficient approach for the high-level production of IL-21 as a biopharmaceutical.

• 한국약용작물학회지
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• 제27권2호
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• pp.143-150
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• 2019

Background: Skin is an organ that protects the human body from various environmental stimuli that can induce immune system activation. Skin aging can be largely divided into two categories: physiological aging, which is caused by the a decreased physiological function of the skin and structural changes with aging, and photoaging, which is caused by the chemical stress induced by external stimuli such as ultraviolet (UV) radiation. Methods and Results: The objective of this study was to investigate the anti-wrinkle and UV protective effect of catechin-rich green tea extract (CGTE) in activated keratinocyte (HaCaT cells) and UV-induced skin damage in hairless mice. The results showed that CGTE inhibits the tumor necrosis factor-alpha interferon-gamma ($TNF-{\alpha}+IFN-{\gamma}$)-induced expression of matrix metalloproteinase (MMP)-1 in HaCaT cells. In addition, the CGTE treatment significantly reduced wrinkle formation, epidermal thickness, collagen deposition, and transepidermal water loss in dorsal skin irradiated with UVB. However, the ${\beta}$-glucosidase activity was significantly increased. The CGTE treatment inhibits mRNA expression and enzyme activity of MMP-2 and MMP-9 in the dorsal skin irradiated with UVB. Conclusions: It is expected that CGTE can be effectively used as a functional food and cosmetic ingredient to improve skin moisture retention and reduce wrinkle formation.

• 대한본초학회지
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• 제34권3호
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• pp.9-17
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• 2019

Objectives : This study was performed to compare the effect of two Cudrania tricuspidata cultivars; Sancheong native (CT) and varieties in china(SCT) on immediate hypersensitivity of the anaphylactic type and Ova-induced allergic asthma mouse model by calculating serum cytokines and IgE. Methods : We investigated the free radical scavanging effect and quantify total phenol contents and total flavonoids of two Cudrania tricuspidata cultivars; Sancheong native(CT) and varieties in china(SCT). The sample was extracted by 80% EtOH. To induce the allergic asthma, in the control group and the CT group, mice of each group were sensitized intraperitoneally with ovalbumin (OVA) solution at the 1st, the 7th and the 14th day. After then, sensitization was performed by aerosol allergen challenges with 1% OVA solution intratracheally at the 21th, the 23th, 25th and the 27th day. At the 29th day, the mice were killed and the changes of interferon-${\gamma}$, interleukin-4, 5 and 10, total IgE and OVA-specific IgE in serum were checked. Results : CT inhibited compound 48/80-induced systemic anaphylaxis 90% with a dose of 100 mg/kg body weight at 1 hr before injection of compound 48/80. In the allergic asthma mouse model, IFN-${\gamma}$ was did not increased in the CT and SCT group than that in the control group. IL-4, IL-5, the total IgE and OVA-specific IgE were decreased in the CT group as compared with the control group and these results were statistically significant. Conclusions : Considering the above experimental results, this study showed that Sancheong native cultivar could reduce the allergic reaction.

• 생명과학회지
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• 제27권5호
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• pp.509-516
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• 2017

들깨(Perilla frutescents (L.) Britton var.) 새싹은 꿀풀과에 속하는 1년생 초본이다. 본 연구의 목적은 들깨 새싹 에탄올 추출물이 사이토카인으로 유도된 췌장 베타 세포 손상에 대한 예방 효과를 평가하기 위함이다. 췌장 소도 주위에 염증 세포 침습으로 의해 분비되는 사이토카인은 1형 당뇨병의 발병원인에 해당된다. 인터루킨-$1{\beta}$ (IL-$1{\beta}$), 인터페론-${\gamma}$ (IFN-${\gamma}$), 종양괴사인자-${\alpha}$ (TNF-${\alpha}$) 등의 사이토카인은 활성산소 형성을 유도한다. 세포 내 활성산소 축적은 췌장 베타 세포 기능장애와 세포사멸을 이끈다. 들깨 새싹 추출물은 항산화 효과를 증가 시켰으며 활성산소 생성을 억제하였다. 사이토카인은 세포생존율을 감소시켰고, iNOS와 COX-2의 발현을 증가시키고 산화질소 생성을 유도하였다. 들깨 새싹 추출물은 사이토카인으로 유도된 세포생존을 농도 의존적으로 예방하였다. 또한, 사이토카인에 의한 산화질소 생성과 iNOS와 COX-2의 단백질 발현 증가를 억제하였다. 더 나아가 들깨 새싹 추출물은 췌장 베타 세포주(RIN-m5F)에서 $I{\kappa}B{\alpha}$ 인산화 억제를 통해서 NF-${\kappa}B$의 활성화를 상당히 감소시켰다. 요약하자면, 본 연구 결과는 들깨 새싹 추출물이 사이토카인으로 유도된 췌장 베타 세포 손상에 대한 보호 효과를 가지고 있다는 것이 확인되었다. 결과적으로 들깨 새싹은 혈당 증가에 의한 산화 스트레스와 염증성 사이토카인에 의한 베타 세포 손상을 완화하여 당뇨에 유익할 것으로 사료된다.

• Journal of Microbiology and Biotechnology
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• 제17권12호
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• pp.2042-2045
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• 2007

The effect of chitosan oligosaccharide (COS, 1 kDa${\gamma}$, 10 ng/ml IL-$1{\alpha}$, and 25 ng/ml TNF-${\alpha}$) in HT-29 cells. Inducible nitric oxide synthase (iNOS) expression induced by these cytokines was inhibited by COS. COS pretreatment inhibited the invasiveness of cytokines-treated HT-29 cells through Matrigel-coated membrane in a dose-dependent manner. COS also inhibited cytokines-induced matrix metalloproteinase (MMP)-2 activity. This study shows that proinflammatory cytokines induce NO production, iNOS expression, and invasiveness of human colorectal adenocarcinoma HT-29 cells. COS pretreatment inhibited cytokines-mediated NO production, iNOS expression, and invasiveness of HT-29 cells. These results provide sufficient information for the further development of COS as an antitumor metastatic agent for the treatment of colon cancer.