• 대한화장품학회지
• /
• 제40권4호
• /
• pp.413-421
• /
• 2014

코르티코트로핀분비인자(Corticotropin-releasing factor)는 스트레스 반응에 관여하는 호르몬으로, 최근 스트레스가 탈모와 같은 피부질환에 영향을 미친다는 보고들이 많아지고 있다. 보고에 따르면, 사람 모낭 배양에서 코르티코트로핀분비인자는 길이생장을 억제하며, 모낭의 조기퇴행을 유도하고 모기질각질형성세포(hair matrix keratinocyte)의 세포사멸을 촉진시킨다. 본 연구에서는 코르티코트로핀분비인자가 모발성장과 모주기조절에 핵심적으로 역할하는 모유두세포에 미치는 영향에 대해 알아보고자 했다. 시상하부-뇌하수체-부신축의 주요 스트레스호르몬들인 코르티코트로핀분비인자, 부신피질자극호르몬, 그리고 코르티솔을 사람 모유두세포에 처리하였다. 흥미롭게도, 코르티코트로핀분비인자가 모발성장과 관련된 사이토카인(KGF, Wnt5a, $TGF{\beta}-2$, Nexin)의 발현을 변화시키는 것을 관찰하였으며, 세포 내 cAMP의 수준을 증가시켰고, 수용체의 발현을 억제시켰다. 이러한 변화는 수용체의 길항제인 antalarmin과 astressin2B, 또는 PKA 억제제의 전처리로 인해 막을 수 있었다. 코르티코트로핀분비인자는 cAMP/PKA경로를 통해 POMC의 발현을 유도하는데, 사람 모유두세포에서도 이 호르몬의 처리가 POMC mRNA의 발현을 증가시키는 것을 확인할 수 있었으나 부신피질자극호르몬의 변화는 western blot으로는 확인할 수 없었다. 이러한 결과들을 바탕으로, 코르티코트로핀분비인자가 그 수용체를 통해 사람 모유두세포 내 모발성장 관련 사이토카인의 발현을 조절함을 확인하였으며, 이는 코르티코트로핀분비인자의 수용체 길항제가 스트레스성 탈모환자를 위한 치료제 혹은 화장품 소재로써 활용될 수 있음을 보여준다.

• 혜화의학회지
• /
• 제22권1호
• /
• pp.145-170
• /
• 2013

Objectives : This study was carried out to investigate the anti inflammatory and anti allergy effects of Vitex rotundifolia Linne fil. extract(VRE). Results : 1. In vitro test, VRE was used to determine the modulation of cytokine secretion, the activation of inflammatory and allergic factor and the inhibition of gene expression. The cell survival rate of Raw 264.7 and Jurkat T cells didn't decrease and accordingly cytotoxicity wasn't observed. In anti-allergic assay, the secretion of IL-2, TNF-${\alpha}$, IL-4, IL-5 and IFN-${\gamma}$ were suppressed on Jurkat T cells induced by dust mites. And the gene expression of COX-2 was suppressed in HMC-1 stimulated by calcium ionophore A23187. In anti-inflammatory assay, the gene expression of TNF-${\alpha}$, COX-2 were suppressed on LPS-activated Raw 264.7 cells. And the secretion of IL-6 and IL-8 were suppressed on EoL-1 cells induced by dust mites. P38 and ERK activation of MAPK decreased generally. VRE showed potent inhibitory activity of NO production. 2. In vivo test, we used NC/Nga mouse induced by atopic dermatitis to observe the effects of VRE on the weight, water and feed, blood test, weight of organs, total IgE and histological change of main organs. Quantity of water and feed were not changed, therefore it didn't affect the weight directly, and no change was observed in related main organs, thus maybe there is no organ toxicity by test substances. And the symptoms were decreased significantly, and the thickness of epithelial cell layer and the number of mast cells were inhibited significantly by the difference of dosage. The number of total complete blood cells and IgE in serum were not changed significantly. Conclusion : These results suggest that VRE has anti-inflammatory and anti-allergic effects. Therefore VRE could be used effectively on improvement or treatment of atopic dermatitis. However, further study is needed to prove which component of VRE indicates effective pharmacological action.

• Journal of Gastric Cancer
• /
• 제4권3호
• /
• pp.149-155
• /
• 2004

Purpose: According to the recent studies, it is shown that the polymorphism of Interleukin $1\beta$ gene is associated with the incidence of gastric cancer caused by the Helicobacter pylori infection. Interleukin $1\beta$ is a cytokine markedly inhibiting gastric acid secretion. Interleukin $1\beta$ production associated with Helicobacter pylori gastric infection may exacerbate mucosal damage including chronic gastritis and atrophic gastritis, may induce eventual neoplasia. Among these Interleukin $1\beta$ gene polymorphisms, polymorphisms at -31 portion and -511 portion may associated with these processes, eventually increase the risk of gastric cancer. We investigated the risk of gastric cancer according to the Helicobacter pylori infection and genetic polymorphism of Interleukin $1\beta$ in gastric cancer patients. Materials and Methods: 176 individuals with gastric cancer and 40 healthy controls were analyzed. Each group was divided into two groups whether they infected with Helicobacter pylori or not. DNA was extracted from the peripheral blood in all groups. The PCR-RFLP method was used for investigating the distribution of genotype of C/C, C/T, T/T at -31 portion and -511 portion. Results: T/T genotype at -511 portion was $19.3\%$ in gastric cancer cases and $10\%$ in controls, which was statistically significant. (P=0.0432) The risk of gastric cancer was increased 4.86 ($1.26\∼18.77$) in group which had T/T genotype. In gastric cancer cases, C/C genotype at 31 portion was $27.6\%$ in group with Helicobacter pylori infection and $12.8\%$ in group without infection, which was statistically significant. (P=0.0047) The risk of gastric cancer was increased 4.82 ($1.81\~12.81$) in group which had C/C genotype. Conclusion: T genotype at -511 portion among the Interleukin $1\beta$ genetic polymorphisms may be the risk factor of gastric cancer. And, with Helicobacter pylori infection, C genotype at -31 portion may be the risk factor of gastric cancer.

• Parasites, Hosts and Diseases
• /
• 제56권4호
• /
• pp.325-334
• /
• 2018

Toxoplasma gondii is an apicomplexan zoonotic protozoan parasite that infects most species of warm-blooded animals, including humans. The heavy incidence and severe or lethal damage caused by T. gondii infection clearly indicate a need for the development of an effective vaccine. T. gondii GRA8 is a member of the dense granules protein family and is used as a marker of acute infection. In the present study, we evaluated the protective immunity induced by DNA vaccination based on a recombinant eukaryotic plasmid, pDsRed2-GRA8, against acute toxoplasmosis in mice. BALB/c mice were intramuscularly immunized with the pDsRed2-GRA8 plasmid and then challenged by infection with the highly virulent GFP-RH strain of T. gondii. The specific immune responses and protective efficacy against T. gondii of this vaccine were analyzed by measuring cytokine and serum antibody titers, splenocyte proliferation assays, and the survival times of mice after challenge. Our results showed that mice immunized with pDsRed2-GRA8 demonstrated specific humoral and cellular responses, induced higher IgG antibody titers with predominant IgG2a production; increased levels of IL-10, IL-12 (p70), $IFN-{\gamma}$, $TNF-{\alpha}$, and splenocyte proliferation; and prolonged survival times compared to those of control mice. The present study showed that DNA immunization with pDsRed2-GRA8 induced humoral and cellular immune responses, and all immunized mice showed greater Th1-type immune responses and longer survival times than those of control mice. These results indicated that T. gondii GRA8 DNA immunization induces a partial protective effect against acute toxoplasmosis.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권18호
• /
• pp.7965-7970
• /
• 2014

One of the goals of tumor immunotherapy is to generate immune cells with potent anti-tumor activity through in vitro techniques using peripheral blood collected from patients. However, cancer patients generally have poor immunological function. Thus using patient T cells, which have reduced in vitro proliferative capabilities and less tumor cell killing activity to generate lymphokine-activated killer (LAK) cells, fails to achieve optimal clinical efficacy. Interleukin-2 (IL-2) is a potent activating cytokine for both T cells and natural killer cells. Thus, this study aimed to identify optimal donors for allogeneic LAK cell immunotherapy based on single nucleotide polymorphisms (SNP) in the IL-2 and IL-2R genes. IL-2 and IL-2R SNPs were analyzed using HRM-PCR. LAK cells were derived from peripheral blood mononuclear cells by culturing with IL-2. The frequency and tumor-killing activity of LAK cells in each group were analyzed by flow cytometry and tumor cell killing assays, respectively. Regarding polymorphisms at IL-2-330 (rs2069762) T/G, LAK cells from GG donors had significantly greater proliferation, tumor-killing activity, and IFN-${\gamma}$ production than LAK cells from TT donors (P<0.05). Regarding polymorphisms at IL-2R rs2104286 A/G, LAK cell proliferation and tumor cell killing were significantly greater in LAK cells from AA donors than GG donors (P<0.05). These data suggest that either IL-2-330(rs2069762)T/G GG donors or IL-2R rs2104286 A/G AA donors are excellent candidates for allogeneic LAK cell immunotherapy.

• 한국자원식물학회지
• /
• 제27권5호
• /
• pp.567-575
• /
• 2014

Resveratrol은 천연 stilbene으로 안전성 있는 항염증 활성을 가진 화합물로 알려져 있다. 최근의 연구들에서 resveratrol이 천식, 만성 대장염, 류마티스성 관절염과 같이 염증에 의해 발생하는 다양한 질병을 억제한다고 보고되었다. 이러한 연구들은 resveratrol이 $CD4^+$ helper T cells (Th cells)에 의한 면역반응을 조절할 것이라고 제시하였다. 그러나 resveratrol이 직접적으로 Th cells의 활성화와 분화를 조절하는지 완전히 밝혀지지 않았다. C57BL/6에서 Th cells을 분리하여 다양한 농도의 resveratrol을 세포에 처리하였다. 본 연구에서는 resveratrol이 직접적으로 Th cells의 활성화와 증식을 억제하는 것을 확인하였다. Th cells에 resveratrol을 처리하였을 때 IFN-${\gamma}$, IL-4, IL-17 사이토카인 생성이 농도에 따라 유의하게 감소하였고 또한 Th cells이 이러한 사이토카인들을 분비하는 Th1과 Th2과 Th17으로 분화되는 것이 억제되었다. 그리고 고농도의 resveratrol이 Th cells의 세포사멸을 유도하는 것으로 확인되었다. 본 연구에서는 resveratrol이 Th cells의 활성화와 분화를 직접적으로 억제하는 것을 확인하였으며, 이는 resveratrol이 $CD4^+$ Thcells에 의해 발생되는 자가면역질환의 효과적인 치료법이 될 수 있을 것이라고 제시한다.

• Preventive Nutrition and Food Science
• /
• 제19권3호
• /
• pp.136-144
• /
• 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. This study was conducted to evaluate the effects of Platycarya strobilacea S. et Z. (PSE) extract on mouse hair growth and to determine the mechanism of action of PSE. PSE was purchased and its antioxidant activities, such as electron donating ability, total polyphenol content, and flavonoid content were tested. Toxicity during topical treatment was determined by the CCK-8 assay, a cell viability test. Fifteen 4-week-old male C57BL/6 mice were assigned to receive one of three treatments: dimethyl sulfoxide (negative control), minoxidil (positive control) or PSE. Test materials were topically applied to the shaved dorsal skin of each mouse daily for 3 weeks. After 21 days, we observed skin tissue hair follicle morphology and length, mast cell number, and stem cell factor (SCF) expression using hematoxylin and eosin (H&E), toluidine blue, and immunohistochemical staining, respectively. Furthermore, the expression of cytokines involved in hair growth [i.e., insulin-like growth factor (IGF)-1, keratinocyte growth factor (KGF), and transforming growth factor (TGF)-${\beta}1$] was determined by PCR. PSE was found to have very high antioxidant activity. The cell viability rate of PSE-treated mice was markedly higher than that of mice in the control group. We also observed an increase in hair follicle length, strong SCF staining, and a decrease in mast cell number in the PSE group. In addition, PSE-treated mice had higher IGF-1 and KGF expression and lower TGF-${\beta}1$ expression than mice in the minoxidil-treated group. These results suggest that topical application of PSE promotes hair growth by intensifying SCF, suppressing mast cell production, and increasing hair growth-promoting cytokine expression.

• Asian-Australasian Journal of Animal Sciences
• /
• 제25권3호
• /
• pp.382-392
• /
• 2012

This study evaluated the effects of dietary anticoccidial drugs plus antibiotic growth promoters (AGPs) on parameters of immunity in commercial broiler chickens. Day-old chicks were raised on used litter from a farm with endemic gangrenous dermatitis to simulate natural pathogen exposure and provided with diets containing decoquinate (DECX) or monensin (COBN) as anticoccidials plus bacitracin methylene disalicylate and roxarsone as AGPs. As a negative control, the chickens were fed with a non-supplemented diet. Immune parameters examined were concanavalin A (ConA)-stimulated spleen cell proliferation, intestine intraepithelial lymphocyte (IEL) and spleen cell subpopulations, and cytokine/chemokine mRNA levels in IELs and spleen cells. ConA-induced proliferation was decreased at 14 d post-hatch in DECX-treated chickens, and increased at 25 and 43 d in COBN-treated animals, compared with untreated controls. In DECX-treated birds, increased percentages of $MHC2^+$ and $CD4^+$ IELS were detected at 14 d, but decreased percentages of these cells were seen at 43 d, compared with untreated controls, while increased $TCR2^+$ IELs were evident at the latter time. Dietary COBN was associated with decreased fractions of $MHC2^+$ and $CD4^+$ IELs and reduced percentages of $MHC2^+$, $BU1^+$, and $TCR1^+$ spleen cells compared with controls. The levels of transcripts for interleukin-4 (IL-4), IL-6, IL-17F, IL-13, CXCLi2, interferon-${\gamma}$ (IFN-${\gamma}$), and transforming growth factor${\beta}$4 were elevated in IELs, and those for IL-13, IL-17D, CXCLi2, and IFN-${\gamma}$ were increased in spleen cells, of DECX- and/or COBN-treated chickens compared with untreated controls. By contrast, IL-2 and IL-12 mRNAs in IELs, and IL-4, IL-12, and IL-17F transcripts in spleen cells, were decreased in DECX- and/or COBN-treated chickens compared with controls. These results suggest that DECX or COBN, in combination with bacitracin and roxarsone, modulate the development of the chicken post-hatch immune system.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권13호
• /
• pp.5181-5186
• /
• 2014

Tumors have evolved numerous mechanisms by which they can escape from immune surveillance. One of these is to produce immunosuppressive cytokines. Transforming growth factor-${\beta}$(TGF-${\beta}$) is a pleiotropic cytokine with a crucial function in mediating immune suppression, especially in the tumor microenvironment. TGF-${\beta}$ produced by T cells has been demonstrated as an important factor for suppressing antitumor immune responses, but the role of tumor-derived TGF-${\beta}$ in this process is poorly understood. In this study, we demonstrated that knockdown of tumor-derived TGF-${\beta}$ using shRNA resulted in dramatically reduced tumor size, slowing tumor formation, prolonging survival rate of tumor-bearing mice and inhibiting metastasis. We revealed possible underlying mechanisms as reducing the number of myeloid-derived suppressor cells (MDSC) and $CD4^+Foxp3^+$ Treg cells, and consequently enhanced IFN-${\gamma}$ production by CTLs. Knockdown of tumor-derived TGF-${\beta}$ also significantly reduced the conversion of na$\ddot{i}$ve $CD4^+$ T cells into Treg cells in vitro. Finally, we found that knockdown of TGF-${\beta}$ suppressed cell migration, but did not change the proliferation and apoptosis of tumor cells in vitro. In summary, our study provided evidence that tumor-derived TGF-${\beta}$ is a critical factor for tumor progression and evasion of immune surveillance, and blocking tumor-derived TGF-${\beta}$ may serve as a potential therapeutic approach for cancer.

• 식품산업과 영양
• /
• 제9권1호
• /
• pp.36-45
• /
• 2004

Bamboo salt has been used for the purpose of prevention and treatment of various diseases in Korea. Present study was carried out to ascertain the effects of purple bamboo salt upon anti-allergic effect, anti-inflammatory activity and immune-enhance effect as well. Purple bamboo salt significantly inhibited the ear swelling response and histamine release induced by compound 48/80 in mice and rat peritoneal mast cells. Purple bamboo salt (0.01 ∼ lg/kg) also dose-dependently inhibited the passive cutaneous anaphylaxis by oral administration. Purple bamboo salt (1 mg/mL) in hibited phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-1${\beta}$ and IL-6 secretion, by 67.04${\pm}$0.08%, 68.01${\pm}$1.85%, 69.48${\pm}$0.54%, respectively. In addition, purple bamboo salt inhibited the expression of TNF-${\alpha}$ mRNA in HMC-1 cells. Finally, we investigated the effect of purple bamboo salt in the forced swimming test (FST) and the change of purple bamboo salt-mediated cytokine production from MOLT-4 cells. At the 7th, immobility time was significantly decreased in the purple bamboo salt-administration group (35.4 ${\pm}$5.9 s for 1 g/kg) in comparison with the control group (93.2 ${\pm}$ 15.45). After FST, the content of glucose in the blood serum was increased and the levels of blood urea nitrogen, lactic dehydrogenase was decreased in purple bamboo salt-administration group. However, it had no effect on the elevation of CK and TP level. Purple bamboo salt (1 mg/mL) significantly increased the interferon (IFN)-${\gamma}$ and IL-2 level compared with media control (about 3.7-fold for IFN-${\gamma}$, about 3.5-fold for IL-2, p〈0.05) but did not affect the IL-4.