결론

Isobavachalcone(IBC)이 LPS에 의해 유도된 세포부착분자 ICAM-1의 발현에 미 치는 영향에 대해 확인한 결과 다음과 같은 결론을 얻었다.

1.LPS에 의해 유도된 내피세포와 백혈구의 부착현상이 IBC에 의해 농도 의존 적으로 감소되었다.

2.LPS에 의해 유도된 세포부착분자 ICAM-1의 발현이 IBC에 의해 농도 의존적 으로 억제되었다.

3.IBC는 LPS에 의해 유도된 NF-kB 활성화를 농도 의존적으로 억제하였다.

4.MyD-88에 의존적인 경로에 특이적인 MALP-2에 의해 유도된 ICAM-1의 발 현이 IBC의 처리에 의해 농도 의존적인 억제 효과를 확인하였다.

5.TRIF에 의존적인 경로에 특이적인 poly[I:C]에 의해 유되된 ICAM-1및 I FN-β의 발현이 IBC에 의해 유의적으로 억제되었으나 농도의존적 억제 양상에는 차 이가 있었다.

따라서 IBC는 TLR 4신호전달계를 억제함으로써 세포부착분자의 발현 및 백혈 구-내피세포부착을 억제함으로써 뇌 염증반응을 개선할 수 있을 것으로 추정되 었다.

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-ABSTRACT-Ef f ectofI BC i sol at edf r om Psor al eacor yl i f ol i aon expr essi on ofadhesi on mol ecul e-1i n

cer ebr ovascul arendot hel i alcel l s

Kwang Min Lee

DepartmentofbiomedicalSciences TheGraduateSchool,Ajou University

(Supervised by AssociateProfessorSooHwan Lee)

Brain inflammation has been implicated in various cerebraldiseases.

Leukocyte-infiltration into brain parenchyma is critically associated with in the development brain inflammation. Therefore, control of leukocyte infiltration is a very important therapeutic target for the treatmentofneurodegenerativediseasesaccompanied with inflammation such as Alzheimer’s disease and stroke. Isobavachalcone (IBC), a flavonoid from Psoralea corylifolia, is known to possess a wide spectrum of biological activities, antibacterial, antifungal, anticancer, anti-reverse transcriptase,antitubercular and antioxidant.Recently,it wasreported thatIBC suppressesLPS-induced iNOS expression and is expected to be useful for preventing or treating neurodegenerative disease.However,the effectof IBC on leukocyte-endothelialadhesion andexpression ofintercellularadhesion molecule-1(ICAM-1)in brain

endothelialcells remains unexplored.In this study,we examined the effect of IBC on ICAM expression and leukocyte adhesion in bEnd.3 cells and explored the possible mechanisms therein involved. IBC significantly down-regulated LPS-induced ICAM-1 expression and leukocytes-endothelialadhesion.IBC suppressed LPS-induced sequential events for NF-kB activation, that is, IkB-α phosphorylation, p65 translocation into nucleus and NF-kB transcriptional activity. TLR4 conveys LPS-signal to intracellular compartment via MyD88- and TRIF-dependentpathways,which culminatein theactivation ofNF-kB.

As well as, IBC attenuated MALP-2 (a TLR2, 6 specific ligand)-induced ICAM-1 expression, IkB-alpha phosphorylation and NF-kB transcriptional activation. suggesting inhibition of MyD88-dependentsignaling pathway.

IBC also down-regulated poly[I:C] (a TLR3 specific ligand)-induced expression ofICAM-1 and IFN-β,which was mediated suppression of NF-kB or IFN-β transcriptional activity, respectively. These data indicate TRIF-dependent signaling pathway is also blocked by IBC.

Taken together, our data suggest that IBC inhibits LPS-induced ICAM-1 expression and leukocyte adhesion in brain endothelialcells and these effects are mediated by blockade of MyD88-dependentand TRIF-dependentsignaling pathways and in turn,inhibition ofNF-kB activity.

Key words : Isobavachalcone(IBC), Lipopolysacharide(LPS), intracellularadhesion molecule 1(ICAM-1),NF-kB,Inteferon-β(IFN-β), cerebrovascularendothelialcells(bEnd.3),Toll-likereceptor4(TLR4)