• 생명과학회지
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• 제20권4호
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• pp.503-510
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• 2010

대부분의 알려진 알러젠들은 단백분해효소의 성격을 가지고 있고 이는 알레르기 반응에서 Th2 면역 반응을 일으키는 데 중요한 역할을 하는 것으로 알려져 있다. 이러한 단백분해효소들과 반응하는 것으로 알려진 protease activated receptor (PAR) 는 4가지 종류가 있으며, 이 중 PAR2의 경우 알레르기 질환과 많은 상관관계를 보여 많은 연구가 되고 있다. 본 연구는 Aspergillus protease 알러젠에 의한 초기 및 만성 Th2 면역반응에서 PAR2 의 역할을 규명하기 위해 Aspergillus protease 알러젠으로 정상쥐와 PAR2 유전자 결핍쥐 모두 Th2 반응을 유도한 후 면역세포의 침윤 정도 및 Th2 관련 cytokine 및 chemokine 유전자들의 발현 정도를 비교하였다. 그 결과 Aspergillus protease 알러젠으로 비강내로 1회 처리했을 경우 중성구의 침윤이 두드러지는데, 이때 PAR2 결핍 마우스는 이러한 면역세포의 침윤이 유의적으로 감소하였다. 또한, 이와 관련된 IL-25, TSLP, Eotaxin 유전자들의 발현 역시 PAR2 결핍 마우스에 현저히 감소하였다. 한편, Aspergillus protease 알러젠으로 비강내로 6회 처리했을 경우 중성구 대신 호산구의 침윤이 두드러지지만 PAR2 결핍 마우스에서 그 정도가 유의적으로 낮았다. OVA 특이 IgE와 IgG1 농도 역시 현저하게 PAR2 결핍 마우스에서 낮았고, CCL21의 발현이 PAR2 결핍마우스 MEF cells에서 현저히 감소하였다. Th2 초기 면역반응에서 가장 중요한 IL-25의 발현에 MAKP p38 pathway가 관여한다는 것을 이번 연구에서 알 수 있다. 본 연구를 통해 Aspergillus protease 알러젠으로 유도된 알러지성 기관지 염증 반응에서 초기 반응뿐만 아니라 만성반응에서도 PAR2가 중요한 것을 알 수 있다.

• Applied Microscopy
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• 제39권2호
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• pp.81-87
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• 2009

당뇨병성 망막증의 당뇨병 합병증의 주요한 증상중의 하나로 망막의 구조적 기능적 변화를 초래한다. 레닌-안지오텐신 시스템은 당뇨병성 망막증의 발병에 주요한 역할을 담당하며 angiotensin I을 angiotensin II로 전환하는 데 담당하는 안지오텐신 전환 효소 (ACE)는 레닌-안지오텐신 시스템의 주요한 요소이다. VEGF는 실명을 일으키는 당뇨병성 망막증의 신생혈관 생성에 관여하는 주요한 인자로 알려져 있다. 따라서 본 연구에서는 당뇨병성 망막증의 발생 기전 중 하나로 최근 연구가 진행되고 있는 VEGF의 발현과 안지오텐신 전환 효소 억제제를 이용한 VEGF 발현 억제효과의 규명을 통해 당뇨병성 망막증의 예방에 ACE 억제제가 효과가 있는지 ACE 억제제인 captopril을 이용하여 알아보고자 하였다. 본 연구에서는 streptozotocin 처리시 혈청내 VEGF 농도는 증가하였으나 captopril (65 mg/kg) 치료에 의해 감소하지 않았다. 망막에서 관찰한 결과 당뇨군에서 VEGF mRNA 및 단백질 발현이 증가하였으며, 안지오텐신 전환 효소인 capto-pril에 의해서 차단되는 것으로 나타났다. 결론적으로 captopril은 1형 당뇨에 있어서 망막의 VEGF 발현 억제를 통해 망막 보호효과를 나타내고 있음을 알 수 있었다.

• 한국임상수의학회지
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• 제23권3호
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• pp.243-250
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• 2006

The chickens fed with the feeds supplemented with green tea(GT) and lactic acid bacteria(LB) were infected orally with 10,000 oocysts per chicken of E. maxima. The groups administered with the feeds supplemented with GT by 0.5% and 2.0% of feed showed the significant levels of decreasing in the number of oocysts shed for 5 days after E. maxima infection. The feeds supplemented with LB by 0.1% and 0.5% of feed were less effective in reducing the number of the fecal oocyst, compared with the groups administered with GT. To evaluate the immunoregulatory effects of the feed additives, the expression patterns of IL-2 and IFN-r in spleen cells were studied by RT-PCR and ELISA. The higher levels of IL-2 transcripts after E. maxima infection were observed in the groups with n, compared with the groups with LB and the mixture of GT and LB. The $IFN-\gamma$ mRNA bands were observed in the all of experimental groups except the uninfected control. The culture supernatants of Con A-stimulated spleen cells($5{\times}10^6cells/ml$) were measured for the concentration of IL-2 and $IFN-\gamma$ by ELISA. The levels of IL-2 and $IFN-\gamma$ on days 3 and 7 after E. maxima infection were significantly augmented in the groups with n. These results indicated that GT-supplemented feeds resulted in higher reduction of oocyst-shedding and more enhanced immune responses in the chicken infected with E. maxima, as compared with LB-supplemented feeds. According to the results, it was implicative that the supplements could be utilized for development of feed additives for anti-coccidiosis.

• BMB Reports
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• 제53권9호
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• pp.478-483
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• 2020

Kudoa septempunctata is a myxozoan parasite that causes food poisoning in individuals consuming olive flounder. The present study aimed to investigate the currently insufficiently elucidated early molecular mechanisms of inflammatory responses in the intestine owing to parasite ingestion. After Kudoa spores were isolated from olive flounder, HT29 cells were exposed to spores identified to be alive using SYTO-9 and propidium iodide staining or to antigens of Kudoa spores (KsAg). IL-1β, IL-8, TNF-α and NFKB1 expression and NF-κB activation were assessed using real-time PCR, cytokine array and western blotting. The immunofluorescence of FITC-conjugated lectins, results of ligand binding assays using Mincle-Fc and IgG-Fc, CLEC4E expressions in response to KsAg stimulation, and Mincle-dependent NF-κB activation were assessed to clarify the early immune-triggering mechanism. Inflammatory cytokines (IL-1β, GM-CSF and TNF-α), chemokines (IL-8, CCL2, CCL5 and CXCL1) and NF-κB activation (pNF-κB/NF-κB) in HT29 cells increased following stimulation by KsAg. The immunofluorescence results of spores and lectins (concanavalin A and wheat germ agglutinin) suggested the importance of Mincle in molecular recognition between Kudoa spores and intestinal cells. Practically, data for Mincle-Fc and KsAg binding affinity, CLEC4E mRNA expression, Mincle immunofluorescence staining and hMincle-dependent NF-κB activation demonstrated the involvement of Mincle in the early immune-triggering mechanism. The present study newly elucidated that the molecular recognition and immune-triggering mechanism of K. septempunctata are associated with Mincle on human intestinal epithelial cells.

• 셀메드
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• 제3권2호
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• pp.18.1-18.7
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• 2013

Inflammation in rheumatoid arthritis is characterized by immune cell infiltration and cytokine secretion. In particular, mast cells and their cytokines play an important role in the pathogenesis of rheumatoid arthritis. Korean medicine, BaekJeol-Tang (BT) was designed by traditional Korean medicine theory. We already reported therapeutic effect of BT in rheumatoid arthritis. Here, we report the specific underlying mechanism of BT in activated human mast cells, HMC-1 cells. In addition, we report for the first time that BT significantly inhibited the production and mRNA expression of proinflammatory cytokines including thymic stromal lymphopoietin, interleukin (IL)-$1{\beta}$, IL-6, IL-8, and tumor necrosis factor-${\alpha}$ in activated HMC-1 cells. BT also decreased the activation of mitogen-activated protein kinases, nuclear factor-${\kappa}B$, and caspapase-1. Taken together, these results indicate that BT has potential as a regulator of inflammatory reactions for the treatment of arthritis such as osteoarthritis and rheumatoid arthritis.

• The Journal of Advanced Prosthodontics
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• 제3권3호
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• pp.152-160
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• 2011

PURPOSE. This study was to investigate the effects of recombinant human platelet-derived growth factor (rhPDGF-BB) and heparin to titanium surfaces for enhancement of osteoblastic functions and inhibition of inflammation activity. MATERIALS AND METHODS. The anodized titanium discs, not coated with any material, were used as a control group. In heparinized-Ti group, dopamine was anchored to the surface of Ti substrates, and coated with heparin. In PDGF-Ti group, rhPDGF-BB was immobilized onto heparinized Ti surface. The surface morphologies were investigated by the scanning electron microscope in each group. The release kinetics of rhPDGF-BB were analyzed, and cytotoxicity tests for each group were conducted. The biocompatibilities were characterized by measuring cell proliferation, alkaline phosphatase activity, and calcium deposition using MG-63 cells. Statistical comparisons were carried out by one-way ANOVA tests. Differences were considered statistically significant at $^*$P<.05 and $^{**}$P<.001. RESULTS. The combination of rhPDGF-BB and heparin stimulated alkaline phosphatase activity and OCN mRNA expression in osteoblastic cells ($^*$P<.05 and $^{**}$P<.001). MG-63 cells grown on PDGF-Ti had significantly higher amounts of calcium deposition than those grown on anodized Ti ($^{**}$ P<.001). Heparinized Ti was more anti-inflammatory compared to anodized Ti, when exposed to lipopolysaccharide using the transcript levels of TNF-${\alpha}$ and IL-6 of proinflammatory cytokine ($^*$P<.05 and $^{**}$P<.001). CONCLUSION. The result of this study demonstrated that the incorporation of rhPDGF-BB and heparin onto Ti surface enhanced osteoblastic functions and inhibited inflammation.

• 대한의생명과학회지
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• 제13권3호
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• pp.161-168
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• 2007

Salicornia herbacea L. (Chenopodiaceae: S. herbacea) is a salt marsh plant, which has long been prescribed in traditional medicines for the treatment of intestinal ailments, nephropathy, and hepatitis in Oriental countries. In order to elucidate the mechanisms of this herb, we conducted an anti-oxidative activity, the inhibition of nitric oxide (NO) production, and the suppression of the pro-inflammatory cytokine genes, with the solvent-extracts of S. herbacea. We found that both ethyl acetate and n-butanol tractions showed potent anti-oxidative effects in comparison to other fractions using xanthine oxidase assay with $IC_{50}$ values of $66.0{\pm}0.5\;{\mu}g/ml$ and $82.5{\pm}3.8\;{\mu}g/ml$, respectively. In addition, both ethyl acetate and n-butanol fractions showed more electron donating activity (EDA) than other tractions, according to DPPH (2, 2-Diphenyl-lpicrylhydrazyl radical) assay. The EDA of ethyl acetate fraction ($IC_{50}$ values of $117.5{\pm}3.8\;{\mu}g/ml$) is more significant than that of n-butanol fraction ($IC_{50}$ values of $375.0{\pm}12.5\;{\mu}g/ml$). Among potential anti-oxidative tractions, ethyl acetate traction dose-dependently suppressed lipopolysaccharide (LPS, $0.1\;{\mu}g/ml$)-induced nitric oxide (NO) production in RAW264.7 cell, while n-butanol did not. As expected, ethyl acetate fraction suppressed the expression of inducible NO synthase (iNOS) in RAW264.7 cell stimulated by $0.1\;{\mu}g/ml$ of LPS. Moreover, the ethyl acetate traction suppressed the expression of interleukin-1 $(IL)-1{\beta}$ and granulocyte/macrophage colony-stimulating factor (GM-CSF) mRNA in LPS-stimulated RAW264.7 cells. Therefore, these results suggest that S. herbacea may have anti-oxidative and anti-inflammatory activities by modulating radical-induced toxicity and various pro-inflammatory responses.

• Asian-Australasian Journal of Animal Sciences
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• 제30권10호
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• pp.1478-1485
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• 2017

Objective: The effects of vaccinating 18-day-old chicken embryos with the combination of recombinant Eimeria profilin plus Clostridium perfringens (C. perfringens) NetB proteins mixed in the Montanide IMS adjuvant on the chicken immune response to necrotic enteritis (NE) were investigated using an Eimeria maxima (E. maxima)/C. perfringens co-infection NE disease model that we previously developed. Methods: Eighteen-day-old broiler embryos were injected with $100{\mu}L$ of phosphate-buffered saline, profilin, profilin plus necrotic enteritis B-like (NetB), profilin plus NetB/Montanide adjuvant (IMS 106), and profilin plus Net-B/Montanide adjuvant (IMS 101). After post-hatch birds were challenged with our NE experimental disease model, body weights, intestinal lesions, serum antibody levels to NetB, and proinflammatory cytokine and chemokine mRNA levels in intestinal intraepithelial lymphocytes were measured. Results: Chickens in ovo vaccinated with recombinant profilin plus NetB proteins/IMS106 and recombinant profilin plus NetB proteins/IMS101 showed significantly increased body weight gains and reduced gut damages compared with the profilin-only group, respectively. Greater antibody response to NetB toxin were observed in the profilin plus NetB/IMS 106, and profilin plus NetB/IMS 101 groups compared with the other three vaccine/adjuvant groups. Finally, diminished levels of transcripts encoding for proinflammatory cytokines such as lipopolysaccharide-induced tumor necrosis $factor-{\alpha}$ factor, tumor necrosis factor superfamily 15, and interleukin-8 were observed in the intestinal lymphocytes of chickens in ovo injected with profilin plus NetB toxin in combination with IMS 106, and profilin plus NetB toxin in combination with IMS 101 compared with profilin protein alone bird. Conclusion: These results suggest that the Montanide IMS adjuvants potentiate host immunity to experimentally-induced avian NE when administered in ovo in conjunction with the profilin and NetB proteins, and may reduce disease pathology by attenuating the expression of proinflammatory cytokines and chemokines implicated in disease pathogenesis.

• 한국발생생물학회지:발생과생식
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• 제3권1호
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• pp.59-67
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• 1999

초기배아의 발생과정동안 배아와 모체에서 발현되는 여러 cytokine은 착상을 위한 신호물질로 중요한 역할을 한다. 그 중 interleukin-1$\beta$ (IL-1$\beta$)는 배아와 모체간의 상호 신호전달체로서 성공적인 착상을 위한 필수적인 요소로 작용한다고 알려져 있다. 따라서 본 연구에서는 초기배아의 발생과정에 있어서 IL-1$\beta$ 유전자의 역할을 규명하기 위해 생쥐 초기배아에서의 IL-l$\beta$ 유전자의 발현양상을 역전사중합효소연쇄반응을 통해 조사하였고, IL-l$\beta$ 유전자의 발현에 미치는 수란관과 자궁내막세포의 영향을 밝혀보기 위해 공배양방법을 이용하였다. 그 결과 IL-l$\beta$ in vivo 에서는 4-세포기부터 포배기까지, in vitro에서는 상실배부터 부화중 포배기까지 발현하는 양상을 보였다. 또한 수란관과 자궁내막세포와의 공배양시 대조군과 비교하였을 때 실험군에서 IL-l$\beta$ 유전자의 발현이 촉진되었다. 이러한 결과는 IL-l$\beta$ 의 존재가 착상전 초기배아의 발생에 중요한 역할을 한다는 것을 의미한다. 또한 수란관과 자궁내막세포와의 공배양을 통해 IL-1$\beta$ 유전자의 발현이 수란관과 자궁요소에 의해 조절됨을 확인하였다.

• 한국식품과학회지
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• 제43권4호
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• pp.458-463
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• 2011

In vivo에서 10주간의 UV 조사에 의해 유발되는 피부 손상 및 2주간의 아세톤 도포에 의해 유발되는 급성 피부장벽손상에 대한 콜라겐 펩타이드의 보호 효능을 관찰한 결과, 주름 증가, 비정상적 각질 세포 증식에 의한 피부 두께 증가, 염증성 사이토카인의 증가 등이 콜라겐 펩타이드의 경구 섭취에 의해 개선됨을 확인하여, 콜라겐 펩타이드가 피부 손상을 방어하고, 피부 장벽회복기능이 정상적으로 작용할 수 있도록 도움을 주는 것을 알 수 있었다. 콜라겐 펩타이드의 피부 장벽 회복 기전을 살펴보기 위하여 사람 각질세포를 이용하여 평가한 결과, 콜라겐 펩타이드는 SPT 발현을 농도 의존적으로 증가시킴을 확인하였으며, 이를 통하여 콜라겐 펩타이드가 광노화 및 급성 피부장벽 손상에 의해 유발되는 피부 진피 및 표피 층의 손상을 회복 혹은 보호하는 효능이 있음을 알 수 있었다. 이상의 결과로부터 콜라겐 펩타이드가 광노화 보호 또는 피부장벽 개선 효능을 갖는 새로운 미용 식품 소재로써 이용 가능성이 높음을 확인할 수 있다.