• Tuberculosis and Respiratory Diseases
• /
• 제78권3호
• /
• pp.218-226
• /
• 2015

Background: Eph receptors and ephrin ligands have several functions including angiogenesis, cell migration, axon guidance, fluid homeostasis, oncogenesis, inflammation and injury repair. The EphA2 receptor potentially mediates the regulation of vascular permeability and inflammation in response to lung injury. Methods: Mice were divided into 3 experimental groups to study the role of EphA2 signaling in the lipopolysaccharide (LPS)-induced lung injury model i.e., IgG+phosphate-buffered saline (PBS) group (IgG instillation before PBS exposure), IgG+LPS group (IgG instillation before LPS exposure) and EphA2 monoclonal antibody (mAb)+LPS group (EphA2 mAb pretreatment before LPS exposure). Results: EphA2 and ephrinA1 were upregulated in LPS-induced lung injury. The lung injury score of the EphA2 mAb+LPS group was lower than that of the IgG+LPS group ($4.30{\pm}2.93$ vs. $11.45{\pm}1.20$, respectively; p=0.004). Cell counts (EphA2 mAb+LPS: $11.33{\times}10^4{\pm}8.84{\times}10^4$ vs. IgG+LPS: $208.0{\times}10^4{\pm}122.6{\times}10^4$; p=0.018) and total protein concentrations (EphA2 mAb+LPS: $0.52{\pm}0.41mg/mL$ vs. IgG+LPS: $1.38{\pm}1.08mg/mL$; p=0.192) were decreased in EphA2 mAb+LPS group, as compared to the IgG+LPS group. In addition, EphA2 antagonism reduced the expression of phospho-p85, phosphoinositide 3-kinase $110{\gamma}$, phospho-Akt, nuclear factor ${\kappa}B$, and proinflammatory cytokines. Conclusion: This results of the study indicated a role for EphA2-ephrinA1 signaling in the pathogenesis of LPS-induced lung injury. Furthermore, EphA2 antagonism inhibits the phosphoinositide 3-kinase-Akt pathway and attenuates inflammation.

• Biomolecules & Therapeutics
• /
• 제24권5호
• /
• pp.529-535
• /
• 2016

Atopic dermatitis (AD) results from gene and environment interactions that lead to a range of immunological abnormalities and breakdown of the skin barrier. Protease-activated receptor 2 (PAR2) belongs to a family of G-protein coupled receptors and is expressed in suprabasal layers of the epidermis. PAR2 is activated by both trypsin and a specific agonist peptide, SLIGKV-$NH_2$ and is involved in both epidermal permeability barrier homeostasis and epithelial inflammation. In this study, we investigated the effect of lobaric acid on inflammation, keratinocyte differentiation, and recovery of the skin barrier in hairless mice. Lobaric acid blocked trypsin-induced and SLIGKV-$NH_2$-induced PAR2 activation resulting in decreased mobilization of intracellular $Ca^{2+}$ in HaCaT keratinocytes. Lobaric acid reduced expression of interleukin-8 induced by SLIGKV-$NH_2$ and thymus and activation regulated chemokine (TARC) induced by tumor necrosis factor-a (TNF-${\alpha}$) and IFN-${\gamma}$ in HaCaT keratinocytes. Lobaric acid also blocked SLIGKV-$NH_2$-induced activation of ERK, which is a downstream signal of PAR2 in normal human keratinocytes (NHEKs). Treatment with SLIGKV-$NH_2$ downregulated expression of involucrin, a differentiation marker protein in HaCaT keratinocytes, and upregulated expression of involucrin, transglutamase1 and filaggrin in NHEKs. However, lobaric acid antagonized the effect of SLIGKV-$NH_2$ in HaCaT keratinocytes and NHEKs. Topical application of lobaric acid accelerated barrier recovery kinetics in a SKH-1 hairless mouse model. These results suggested that lobaric acid is a PAR2 antagonist and could be a possible therapeutic agent for atopic dermatitis.

• 생명과학회지
• /
• 제22권5호
• /
• pp.595-599
• /
• 2012

최근 알러지성 비염, 알러지성 피부염, 알러지성 천식, 알러지성 과민반응 등과 같은 질병이 점차 늘어나고 있으며 그에 따른 효과적인 치료제나 효율적인 치료법이 시급한 실정이다. 본 연구에서 동물모델과 비만세포 탈과립작용에서 Platycodin D가 포함된 도라지 추출물(PG-Platycodin D)의 항알러지 효과를 연구하였다. $In$ $vivo$ 상에서 PG-Platycodin D가 항원-항체 반응에 의한 알러지 반응을 효과적으로 억제하는지 살펴보기 위한 아나필락틱 쇼크 평가에서 Platycodin D의 함량이 1%에서 5%까지 증가한 도라지 추출물일수록 $in$ $vivo$ 수준에서의 알러지반응이 억제되는 것을 확인할 수 있었다. 또한 항원-항체 반응에 의해 매개된 RBL-2H3 비만세포의 탈 과립현상에 대한 PG-Platycodin D의 효과를 알아보기 위한 ${\beta}$-hexosaminidase의 방출량 측정에서 Platycodin D의 함량이 1%에서 5%까지 포함된 도라지 추출물에서 농도가 증가함에 따라 ${\beta}$-hexosaminidase의 방출량이 농도 의존적으로 감소하는 것을 알 수 있었다. 또한, PG-Platycodin D의 처리가 항원-항체 반응에 의해 매개된 RBL-2H3 비만세포 내의 IL-3의 발현이 감소하는 양상을 확인할 수 있었다. 이들의 결과로부터 Platycodin D가 포함된 도라지 추출물이 IL-3의 유전자 발현을 억제함으로써 항원-항체 반응에 의한 탈 과립현상을 억제하여 알러지 작용을 제어하는 가능성을 확인하였다.

• 경영과정보연구
• /
• 제31권2호
• /
• pp.253-272
• /
• 2012

본 연구는 컨벤션 참가자들의 심리적인 가치추구과정을 분석하여 관광컨벤션산업을 중심으로 지역 발전을 계획하는 지방정부에게 컨벤션개최지의 이상적인 브랜드가치 개발에 대한 중요한 시사점을 제시하는데 연구의 목적이 있다. 먼저 본 연구를 통해서 밝혀진 컨벤션개최지의 속성으로는 정보성, 경제성, 관광 매력성, 활동성, 자연성 등이 도출되었다. 아울러 이러한 속성들로부터 컨벤션참가자들이 얻고자 하는 주요결과(consequences)로는 공유 공감, 인간관계, 조화로움, 안전, 즐거움, 간접 이미지 등 14개가 도출되었다. 마지막으로 컨벤션 개최지 방문객들이 얻고자 하는 궁극적인 가치들로는 자아발전, 유대감 형성, 자기이익추구, 자존감 고양이 주요 가치(value)요소들로 도출되었다. 연구결과를 살펴보면, 완성된 가치 계층 사슬 지도에서 주요 속성 두 가지(정보성, 활동성)를 선택한 방문객들은 공통적으로 공유 공감을 할 수 있으며 새롭고 나에게 도움을 주는 사람과 인간관계를 형성할 수 있다는 점을 중요한 혜택이라고 응답하였으며, 최종적으로 자아발전과 유대감 형성이라는 가치(value)요소와 직접적으로 가장 많이 연결되어 있음이 밝혀졌다. 그 외에도 인간관계가 자기이익추구에 궁극적으로 도움이 되는 중요한 가치로 여긴다는 연구결과도 밝혀졌다.

• 한국자원식물학회지
• /
• 제29권5호
• /
• pp.532-538
• /
• 2016

난소의 노화에 의해 폐경이 시작되면 에스트로겐 분비가 중단되어 여러 폐경 증상들을 겪게 되는데 이것으로 인해 발병되는 성인병 질환에 대한 치료 또는 예방에 대한 연구가 활발히 진행되고 있다. 본 연구의 목적은 난소절제술을 통해 폐경을 유도한 흰 쥐 모델에서 골담초 열수 추출물의 체내 물질 대사 관련 여부 및 개선 효과를 검토하기 위하여 실험을 수행하였다. Sprague-Dawley 암컷 쥐30마리를 비절제난소군(SHAM), 난소제거군(OVX) 그리고 골담초 추출물을 급여한 OVX-CS군으로 각각 10리씩 나누어 8주간 사육하였다. 체중 및 체중증가량 그리고 지방조직무게는 OVX군에서 유의적으로 증가하였으며 OVX-CS 군에서 감소하였다. 에스트로겐 결핍으로 인한 혈장 중성지질, 총콜레스테롤 수준은 골담초 추출물 급여에 따라 감소하고 HDL 콜레스테롤 수준은 증가하였다. 또한 지방산 합성 관련 효소 활성도인 ME는 간조직에서는 OVX-CS군에서 유의적으로 감소하였고 G6PD 활성은 OVX 군들 간에는 차이가 없었다. 당신생합성 관련 효소인 G6pase 활성은 골담초 추출물 섭취에 따라 억제되는 것으로 나타났다. 혈장 아디포카인 측정 결과 렙틴 농도는 OVX-CS군이 정상군 수치만큼 감소하였으며, 아디포넥틴도 정상수준으로 증가하였다. 이상의 결과로 난소제거를 통해 폐경이 유도된 흰쥐모델에서 골담초 추출물 급여가 에스트로겐 결핍으로 인한 체중증가를 억제하고, 지질 및 당질 대사에 긍정적인 영향을 미쳐 건강기능성 소재로서의 가능성이 높은 것으로 보이며, 추후 골담초의 구체적인 생활성물질을 추적하여 그 과학적 기전을 밝히는 것이 필요하다고 판단된다.

• 한국수정란이식학회:학술대회논문집
• /
• 한국수정란이식학회 2002년도 국제심포지엄
• /
• pp.97-97
• /
• 2002

Human eryhropoietin (EPO) is acidic glycoprotein hormone that plays key role in hematopoiesis by facilitating differentiation of erythrocyte and formation of hemoglobin (Hb) and is used for the treatment of anemia. Human EPO is consist of 166 amino acids which is modified by three N-glycosylations (24, 38, 83) and single O-glycosylation (126). N-glycosylation is reported to be related to the cellular secretion and activity of EPO. In this study, we examined effects of mutagenesis in glycosylation site of recombinat hEPO for the cellular secretion during production from cultured CHO cell. We produced rhEpo which was cloned by PCR from human liver cDNA (TaKaRa) in cultured CHO cell. Using supernatant of the culture, ELISA assay and western analysis were performed. To estimate biological activity, 20IU of rhuEpo was subcutaneously injected into four ICR mice. After 8 days, HCT level was increased average 13 per cent, RBC was increased ca. 2${\times}$10$\^$6//${\mu}\ell$. In disease model Rat (anemia c-kit, WSRC-WS/WS), HCT was increased ca. 12%, RBC was increased ca. 1.6${\times}$10$\^$6//${\mu}\ell$. These results suggests that rhEpo we produced has biological activity. To remove glycosylation site by substituting 24, 38, 83, and 126th asparagine (or serine) with glutamic acid, overlapping -extension site-directed mutagenesis was performed. To add novel glycosylation sites, 69, 105th leucine was mutated to asparagine. Mutant EPO construct was transfected into CHO cell. Supernatant of the cell culture was analyzed using ELISA assay with monoclonal anti-EPO antibody (Medac, Germany). Since, several reports for mutagenesis of glycosylation sites showed case-by-case results, we examined both transient expression and stable expression. Addition of novel glycosylation sites resulted no secretion while deletion mutants had little effect except some double deletion mutants (24/83 and 38/83) and triple mutant. We suggest that not single but combination of glycosyl group affect secretion of EPO.

• 대한한방내과학회지
• /
• 제29권3호
• /
• pp.629-640
• /
• 2008

Objective : The purpose of this study was to investigate the neuroprotective effect of Jukryuk on 4-vessel occlusion(4-VO) and middle cerebral artery (MCA) ischemia. Method : After administration of Jukryuk, we compared the Jukryuk-treated group, the control, and the sham groups, in view of several points as follows 1) We evaluated the damage characterized by coagulative cell change of pyramidal neurons and pronounced gliosis in each group 2) We counted the number of normal pyramidal shapes after ischemia in each group 3) Immunohistochemistry (cyclooxygenase-2) 4) In focal ischemic injury model, we measured the volume of ischemic area Results : In this experiment, the effect of Jukryuk was determined to be protecting neuron cell shape, reducing the number of neuron cells damaged by ischemia and the volume of the ischemic area. In immunohistochemistry, Jukryuk reduced cyclooxygenase-2 expression Conclusions : According to this study, Jukryuk can protect neuron cells from injury by cerebrovascular ischemia.

• Nutrition Research and Practice
• /
• 제4권5호
• /
• pp.362-368
• /
• 2010

Oral administration of royal jelly (RJ) promotes wound healing in diabetic mice. Concerns have arisen regarding the efficacy of RJ on the wound healing process of normal skin cells. In this study, a wound was created by scratching normal human dermal fibroblasts, one of the major cells involved in the wound healing process. The area was promptly treated with RJ at varying concentrations of 0.1, 1.0, or 5 mg/ml for up to 48 hrs and migration was analyzed by evaluating closure of the wound margins. Furthermore, altered levels of lipids, which were recently reported to participate in the wound healing process, were analyzed by HPTLC and HPLC. Migration of fibroblasts peaked at 24 hrs after wounding. RJ treatment significantly accelerated the migration of fibroblasts in a dose-dependent manner at 8 hrs. Although RJ also accelerated the migration of fibroblasts at both 20 hrs and 24 hrs after wounding, the efficacy was less potent than at 8 hrs. Among various lipid classes within fibroblasts, the level of cholesterol was significantly decreased at 8 hrs following administration of both 0.1 ug/ml and 5 mg/ml RJ. Despite a dose-dependent increase in sphinganines, the levels of sphingosines, ceramides, and glucosylceramides were not altered with any concentration of RJ. We demonstrated that RJ enhances the migration of fibroblasts and alters the levels of various lipids involved in the wound healing process.

• 대한본초학회지
• /
• 제23권4호
• /
• pp.39-44
• /
• 2008

Objectives: Notopterygium incisum(N. incisum) and Saposhnikovia divaricata(S. divaricata) have been clinically used in traditional oriental medicine for treatment of inflammatory diseases. Also, a herbal mixture prepared with N. incisum and S. divaricata has been strongly linked to the anti-inflammatory effect. In this study, we evaluate the synergistic anti-inflammatory effect of N. incisum and S. divaricata. Methods: For evaluating the anti-inflammatory activity of a herbal mixture of N. incisum and S. divaricata in vivo, we measured the changed ear thickness in 12-O-tetradecanoyl-phorbol-13-acetate(TPA)-induced mouse ear edema model after topical application of herbal mixture. In addition, the levels of markers for inflammation, such as tumore necrosis factor (TNF)-${\alpha}$, interleukin (IL)-1${\beta}$, and nitric oxide(NO), were determined by ELISA assay in lipopolysaccharide-stimulated Raw 264.7 cells. Results: We reported that water extracts of N. incisum and S. divaricata combination significantly inhibited the mouse ear edema induced by TPA. Moreover, the water extracts of N. incisum and S. divaricata combination exhibited synergistic effects in down-regulating IL-1${\beta}$ level, but not TNF-${\alpha}$ and NO. Conclusions: These results suggest that combined treatment of N. incisum and S. divaricata, based on seven methods in prescription compatibility, has a synergistic effect in down-regulating inflammatory response both in vivo and in vitro models. Especially, it seems that IL-1${\beta}$ is a one of main target of the mixture of N. incisum and S. divaricata on anti-inflammatory activity.

• The Korean Journal of Physiology and Pharmacology
• /
• 제20권1호
• /
• pp.83-89
• /
• 2016

Sepsis is the life-threatening response to infection which can lead to tissue damage, organ failure, and death. In the current study, the effect of orally administered D-glucose on the mortality and the blood glucose level induced by D-Galactosamine (GaLN)/lipopolysaccharide (LPS)-induced sepsis was examined in ICR mice. After various amounts of D-glucose (from 1 to 8 g/kg) were orally fed, sepsis was induced by injecting intraperitoneally (i.p.) the mixture of GaLN /LPS. Oral pre-treatment with D-glucose dose-dependently increased the blood glucose level and caused a reduction of sepsis-induced mortality. The oral post-treatment with D-glucose (8 g/kg) up to 3 h caused an elevation of the blood glucose level and protected the mortality observed in sepsis model. However, D-glucose post-treated at 6, 9, or 12 h after sepsis induction did not affect the mortality and the blood glucose level induced by sepsis. Furthermore, the intrathecal (i.t.) pretreatment once with pertussis toxin (PTX; $0.1{\mu}g/5ml$) for 6 days caused a reduction of D-glucose-induced protection of mortality and hyperglycemia. Furthermore, once the hypoglycemic state is continued up to 6 h after sepsis initiated, sepsis-induced mortality could not be reversed by D-glucose fed orally. Based on these findings, it is assumed that the hypoglycemic duration between 3 and 6 h after the sepsis induction may be a critical time of period for the survival. D-glucose-induced protective effect against sepsis-induced mortality appears to be mediated via activating PTX-sensitive G-proteins in the spinal cord. Finally, the production of hyperglycemic state may be critical for the survival against the sepsis-induced mortality.