• Tuberculosis and Respiratory Diseases
• /
• 제56권4호
• /
• pp.364-373
• /
• 2004

연구배경 : 폐쇄성 수면 무호흡 증후군은 고혈압과 심부정맥 및 허혈성 심질환 등의 심혈관질환을 일으키는 위험요소로 알려져 있으나 정확한 기전에 대해서는 아직 확실히 밝혀져 있지 않다. 최근에 soluble intercellular adhesion molecule-1(sICAM-1)과 vascular endothelial growth factor(VEGF)가 죽상경화증의 발생과 진행에 관여한다고 알려지면서, 일부 연구에서는 이러한 사이토카인이 폐쇄성 수면 무호흡 증후군에서도 증가한다고 보고하였다. 저자는 폐쇄성 수면 무호흡 증후군 환자에서 sICAM-1과 VEGF의 농도 변화를 관찰함으로써, 이들 환자에서 동반될 수 있는 심혈관질환 발생의 병태생리를 일부 이해하고자 하였다. 방 법 : 폐쇄성 수면 무호흡 증후군을 진단하기 위해 가톨릭대학교 성바오로병원 수면장애크리닉을 방문하여 수면다원검사를 시행한 37명을 대상으로 하였다. 철야 수면다원검사를 종료한 직후 혈액 채취를 한 후 혈청분리를 하여 $-70^{\circ}C$ 냉장고에 보관하였다. 사이토카인의 측정은 ELISA 방법으로 시행하였고 수면다원검사의 각 지표와 혈청 sICAM-1 농도 및 혈청 VEGF 농도와의 상관 관계를 비교 분석하였다. 결 과 : 무호흡-저호흡지수와 혈청 sICAM-1 농도 사이에는 유의한 상관관계가 없었지만(r=0.27, P>0.05), 무호흡-저호흡지수와 혈청 VEGF 농도는 유의한 상관관계가 있었다(r=0.50, P<0.01). 무호흡지수와 혈청 sICAM-1 농도는 다소 유의한 상관관계가 있었으며(r=0.31, P<0.01) 무호흡지수와 혈청 VEGF 농도 사이에는 유의한 상관관계가 있었다(r=0.45, P<0.01). 결 론 : 폐쇄성 수면 무호흡 혹은 저호흡은 혈청내 sICAM-1 및 VEGF 농도를 증가시키는 것을 알 수 있었으며, 이러한 사이토카인의 발현 증가는 폐쇄성 수면무호흡 증군 환자에서 심혈관질환의 발생에 관련이 있을 것으로 추측된다.

• 한국해양바이오학회지
• /
• 제2권4호
• /
• pp.250-256
• /
• 2007

1. 천연자원으로부터 ICAM-1과 LFA-1 매개성 세포접착 저해제를 탐색한 결과, 초두구 에탄올 추출물은 이에 대한 저해 활성을 나타내었다. 2. 초두구로부터 세포 접착 인자 활성에 관한 물질을 분리 정제하기 위하여, 각종 용매추출과 컬럼 크로마토그래피를 이용하여 얻은 화합물 1과 2로 세포접착인자 저해활성을 확인하였다. 3. 분리된 화합물 1과 2의 sICAM-1과 THP-1 세포와의 결합저해활성 측정 결과, $IC_{50}$ 값은 각각 $7.59{\mu}g/m{\ell}$ 및 $6.98{\mu}g/m{\ell}$로 측정되었다. 실험에 사용된 농도에서는 세포독성을 보이지 않았다. 4. 분리된 화합물 1과 2의 CHO-ICAM-1과 THP-1 세포간의 결합저해활성을 측정한 결과, $IC_{50}$ 값이 각각 $6.7{\mu}g/m{\ell}$ 및 $5.5{\mu}g/m{\ell}$로 측정되었다. 5. 이상의 실험 결과로 미루어 보아, 초두구로부터 분리한 비환식 트리테르페노이드계 화합물들은 세포 접착인자에 대한 저해활성을 가지고 있다고 볼 수 있으며 이 기전을 통하여 생길 수 있는 질환에 대한 치료제 개발에 유효할 것이다. 특히 동맥경화에 대해서는 새로운 기전으로 접근하고 있으므로 기존의 치료제들의 작용기작과는 다른 약품의 개발이 기대된다. 또한 ICAM-1은 염증반응 및 암의 전이에도 관련되어 있으므로, 동맥경화 관련 질환이외에도 다양한 질환에 대한 의약품으로의 응용도 기대된다.

• 환경생물
• /
• 제27권1호
• /
• pp.88-94
• /
• 2009

안토시아닌(Anthocyanin)은 플라보노이드계 화합물의 한 부류로 항산화, 항암 및 항궤양, 항당뇨, 중금속해독, 시력보호, 콜레스테를 저하 등의 다양한 생리활성을 가지는 것으로 보고되어 있다. 죽상경화과정은 염증성 사이토카인의 분비 또는 혈관손상으로 인한 백혈구의 부착과 이동을 통해 시작된다. 본 연구는 이러한 죽상경화의 초기과정에서 안토시아닌 혼합물 중 single compound인 delphinidin chloride (DC) 인간혈관 내피세포주(HUVEC, human umbilical vein endothelial cell line)에서 백혈구 부착과 관련이 있는 ICAM-1 (Intraceliular Adhesion Molecule-1)과 VCAM-1 (Vascular Adhesion Molecule-1) 발현에 미치는 영향에 대해 조사하였다. 세포독성이 없는 농도에서 TNF-$\alpha$에 의해 유도된 혈관 내피세포에 대한 단핵구의 부착정도를 측정하기 위해 monocyte-endothelial cell adhesion assay와 광학현미경을 이용한 형태학적 관찰을 한 결과 DC가 처리농도 의존적으로 부착을 억제하였다. 내피세포로부터 TNF-$\alpha$에 의해 유도된 세포부착 분자인 VCAM-1과 ICAM-1의 발현에 대한 영향을 western blot analysis 및 RT-PCR방법으로 비교 분석한 결과 VCAM-1과 ICAM-1의 단백질과 mRNA수준에서의 발현이 농도 의존적으로 감소되었다. 이러한 결과들을 종합해 볼 때 안토시아닌 중에서 DC를 실험한 결과 DE는 TNF-$\alpha$에 의해 유도된 내피세포의 ICAM-1과 VCAM-1 발현 억제효과를 확인할 수 있었다.

• 대한바이러스학회지
• /
• 제26권1호
• /
• pp.47-58
• /
• 1996

Histopathological vascular changes in hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus include increased vascular permeability, disseminated intravascular coagulation, thrombocytopenia and changes in coagulation activity. Although vascular endothelial cells of main target organs such as kidney infected with Hantaan virus are not damaged but swelling of endothelial cells, perivascular exudates and infiltration of mononuclear cells and fresh interstitial hemorrhages are common. However, the pathogenesis of cell infiltration and hemorrhages around vascular endothelial cells are not well understood. Some endothelial cell molecules or vascular adhesins that acts as adhesion moleulces for leukocyte are expressed on endothelial cells close to site of inflammation. However, whether the expression of endothelial adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule (ICAM-1) and endothelial leukocyte adhesion molecule (ELAM) on vascular endothelial cells are increased by infection with Hantaan virus has not been studied. In this study, the relationship between the expression of VCAM-1, ICAM-1 and ELAM and adhesion of mononuclear cells on endothelial cells of human blood vessels infected with Hantaan virus was investigated. The endothelial cells of umbilical vein was passaged three times in culture medium and the monolayered cells were infected with $10^5\;pfu/ml$ of Hantaan virus grown in Vera E6 cell cultures. The multiplication of virus in cultured endothelial cells was monitored by immunohistochemistry and the expression of adhesion molecules was demonstrated by immunohistochemistry using monoclonal antibodies against VCAM-1, ICAM-1 and ELAM. And in situ hybriditation against ICAM-1 was also performed. The endothelial adhesion molecules, VCAM and ICAM, were expressed after 6 hours postinfection, respectively, and their expressions lasted for 72 hours. Similar expression of VCAM and ICAM appeared on endothelial cells by infection with virus, but the expression of ELAM was not recognized up to 72 hours postinfection. Microscopically, it was noted that many monocuclear cells adhered on endothelial cells infected with viruses. In an electronmicroscopic study, the transendothelial migration of mononuclear cells was observed on monolayered endothelial cells infected with virus. This results suggested that the endothelial adhesion molecules, particulary VCAM and ICAM, might be expressed on endothelial cells by infection with Hantaan virus and these molecules play a key role in the adhesion and extravasation of inflammatory cells around blood vessels.

• 생명과학회지
• /
• 제23권10호
• /
• pp.1199-1208
• /
• 2013

Fibroblastic reticular cells (FRC)는 림프절 T세포 지역에 구조적 골격 형성을 하며 유입 T 세포의 안내길을 제공한다. FRC는 림프절에서 T세포 생물학 발달에 기여한다. 따라서, 이것이 FRC와 T세포 사이에서 FRC의 세포생물학적 근본 기능을 알아보게 하였다. FRC 배양 상등액은 T세포 사멸을 저해하였다. FRC 상등액은 doxorubicin에 대하여 T세포에 Bcl-xL의 발현을 증가시켰다. FRC와 T세포의 공배양은 FRC의 액틴 골격의 변화와 형태적 변화를 유도하였다. 또한, FRC와 T세포의 공배양은 T 세포가 FRC 단일층에 부착하는 결과를 유도하였고 막결합형 intercellular adhesion molecule (ICAM)-1 단백질의 발현은 약간 증가한 반면 용해성 ICAM-1 (sICAM-1) 발현은 시간 의존적으로 드라마틱하게 증가하였다. FRC는 T세포에 의해 분비되는 tumor necrosis factor (TNF) 패밀리들에 의해 CCL5, CXCL1, CXCL5, CXCL16, CCL8, CXCL13와 같은 케모카인들과 ICAM-1 그리고 MMPs의 발현량을 증가시켰다. $TNF{\alpha}$가 FRC에 처리 되었을때 $NF{\kappa}B$ canonical pathway의 RelA는 핵으로 전좌 되었지만, agonistic anti-$LT{\beta}R$ antibody로 처리된 FRC에서 non-canonical $NF{\kappa}B$ pathway의 RelB의 카운터 파트너인 p100의 분해산물 p52는 핵주변부로 축적되었다. 결론적으로 FRC는 FRC와 T세포 양방향 협력을 통해 T세포 생물학적 기능을 증진한다. 이러한 상호협력 관계는 면역반응 동안 조직의 통합성과 기능을 유지하는데 도움을 줄 것으로 사료된다.

• 대한한방내과학회지
• /
• 제41권4호
• /
• pp.668-675
• /
• 2020

Objectives: The aim of this study was to compare the effects of Galkunhwanglyeonhwanggum-tang (GGT), and Sopunghwalhyeol-tang (SPT) on gene expression of MCP-1, ICAM-1, VCAM-1, and eNOS in human umbilical vein endothelial cells (HUVECs). Methods: HUVECs were treated with GGT and SPT at concentrations of 50, 100, and 200 ㎍/mL. Gene expression of MCP-1, ICAM-1, VCAM-1, and eNOS in HUVECs was analyzed by the polymerase chain reaction (PCR), and electrophoresis was performed to verify the gene expression level. Results: 1. MCP-1 gene expression was more strongly decreased by SPT than by GGT. 2. ICAM-1 and VCAM-1 gene expressions were more strongly decreased by SPT than by GGT 3. GGT significantly increased eNOS gene expression, but SPT did not. Conclusions: These findings suggest that GGT and SPT regulate gene expression related to anti-inflammatory effects in HUVECs. Clinical application of these Korean medicines to diseases related to dyslipidemia, such as cardiovascular disease, will require additional in vivo experiments to verify the anti-inflammatory effects of GGT and SPT.

• 대한한의학회지
• /
• 제21권3호
• /
• pp.40-50
• /
• 2000

Objectives : The progression of renal disease can be identified as a glomerulosclerosis by histological examination, and the basic mechanism of glomerulosclerosis is mesangial cell proliferation and mesangial matrix accumulation. ICAM-1, ${\beta}1-integrin$ and MHC-class II are known to attribute to the progression of glomerulosclerosis. They mediate cell-cell or cell-matrix interactions and are expressed in response to injury and inflammation. Up to now, there have been few satisfactory regimens to treat glomerular diseases except minimal change nephrotic syndrome, which can be improved by steroid therapy. Studies were performed in order to investigate whether Jinmu-tang has suppressive effects on some factors associated with the progression of glomerular disease, mesangial cell proliferation, fibronectin synthesis, ICAM-1, ${\beta}1-integrin$ and MHC-class II expression. Methods : Studies were performed with the method of surface enzyme immunoassays or flow cytometry after addition of peripheral blood mononuclear cells(PBMC) supernatants treated with Jinmu-tang, using the cultured human mesangial cells. Results : 1. The suppressive effect of Jinmu-tang on mesangial cell proliferation was higher than that of hydrocortisone. 2. Jinmu-tang has some suppressive effects on fibronectin synthesis, ICAM-1, expression, ${\beta}1-integrin$ expression and MHC-class II expression of mesangial cells, but was lower than hydrocortisone. Conclusions : Jinmu-tang generally shows some immunosuppressive effects. We carefully suggest that the above prescription may be applied to prevent the progression of renal disease or can be used as an adjuvant of or a substitute for steroid therapy.

• The Korean Journal of Physiology and Pharmacology
• /
• 제9권2호
• /
• pp.109-115
• /
• 2005

Endothelial activation and subsequent recruitment of inflammatory cells are important steps in atherogenesis. The increased levels of cell adhesion molecules (CAM) have been identified in diabetic vasculatures, but the underlying mechanisms remain unclear. To determine the relationship among vascular production of superoxide, expression of CAM and diabetes, superoxide generation and expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E- and P-selectin in the aorta from control (C57BL/6J) and diabetic mice (ob/ob) were measured. In situ staining for superoxide using dihydroethidium showed an increased superoxide production in diabetic aorta, accompanied with an enhanced NAD(P)H oxidase activity. Immunohistochemical analysis revealed that the endothelial expression of ICAM-1 ($3.5{\pm}0.4$) and VCAM-1 ($3.8{\pm}0.3$) in diabetic aorta was significantly higher than those in control aorta ($0.9{\pm}0.5$ and $1.6{\pm}0.3$, respectively), accompanied with the enhanced expression of gp91phox, a membrane subunit of NAD(P)H oixdase. Furthermore, there was a strong positive correlation (r=0.89, P＜0.01 in ICAM-1 and r=0.88, P＜0.01 in VCAM-1) between ICAM-1/VCAM-1 expression and vascular production of superoxide. The present data indicate that the increased production of superoxide via NAD(P)H oxidase may explain the enhanced expression of CAM in diabetic vasculatures.

• BMB Reports
• /
• 제49권1호
• /
• pp.57-62
• /
• 2016

Up-regulation of adhesion molecules plays an important role in the infiltration of leukocytes into the skin during the development of various inflammatory skin diseases, such as atopic dermatitis. In this study, we investigated the modulatory effects of 2,3-dimethoxy-2′-hydroxychalcone (DMHC) on tumor necrosis factor (TNF)-α-induced intercellular adhesion molecule-1 (ICAM-1) expression and monocyte adhesiveness, as well as the molecular mechanisms underlying its action in the HaCaT human keratinocyte cell line. Pre-treating HaCaT cells with DMHC significantly suppressed TNF-α-induced ICAM-1 expression and subsequent monocyte adhesiveness. DMHC inhibited TNF-α-induced activation of NF-ᴋB. In addition, DMHC induced HO-1 expression as well as NRF2 activation. Furthermore, HO-1 knockdown using siRNA reversed the inhibitory effect of DMHC on TNF-α-induced ICAM-1 expression and adhesion of monocytes to keratinocytes. These results suggest that DMHC may inhibit TNF-α-induced ICAM-1 expression and adhesion of monocytes to keratinocytes by suppressing the signaling cascades leading to NF-ᴋB activation and inducing HO-1 expression in keratinocytes. [BMB Reports 2016; 49(1): 57-62]

• 사상체질의학회지
• /
• 제12권2호
• /
• pp.171-183
• /
• 2000

1. Back ground and purpose An experimental study has done to examine the effect of defense and cure gastric mucasal damage of Mokdan-pijihwang-tang. 2. Methods Mice had intragastric injected with MJ extract before indomethacin treatment which induces homorrhage infarct and erosion artificially. Degree of lipid peroxidation, general morphology, change of mucous cell, the distribution of PNA, ICAM and distribution of apoptotic cell were objected. (Abbreviation) MJ : Mokdanpijihwang-tang, PNA : Peanut Agglutinin, ICAM : Intercellular Adhesion Molecule 3 Results 1) The degree of lipid peroxidation in INDO-group had increased conspicuously than control group. But the degree of lipid peroxidation in MJ-group had decreased than INDO-group and these decline had probability. 2) After indomethacin treatment, hemorrhage infarct and erosion had increased in stomach body. But in MJ-group, the configuration is normal, except the group intragastric injected with MJ extract at hour 24 before indomethacin treatment. 3) Surface mucous cell and neck mucous had disappeared in INDO-group. But in MJ-group tormal distribution had shown like control group except the group intragastric injected with MJ extract at hour 24 before indomethacin treatment. 4) PNA positive reaction had not shown in INDO-group. But medium PNA positive reaction had shown In Mj-group. 5) ICAM positive reacted cell had shown in INDO-group. The decrease of ICAM positive cell were shown than INDO-group. 6) A number of apoptotic cell was distributed in hemorrhagic erosion. A few number of apoptotic cell was distributed in MJ-group except some surface mucous. 4. Conclusion These results suggest that MJ has an effect on cure of gastric mucosal damage.