Effect of IBC isolated from Psoralea corylifolia on expression of adhesion molecule-1 in cerebrovascular endothelial cells

Brain inflammation has been implicated in various cerebral diseases. 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 treatment of neurodegenerative diseases accompanied 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 was reported that IBC suppresses LPS-induced iNOS expression and is expected to be useful for preventing or treating neurodegenerative disease. However, the effect of IBC on leukocyte-endothelial adhesion and expression of intercellular adhesion molecule-1(ICAM-1) in brain endothelial cells 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-endothelial adhesion. 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,whichculminateintheactivationofNF-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 ofMyD88-dependentand TRIF-dependentsignaling pathways and in turn,inhibition ofNF-kB activity.

Author dc:creator

• 이, 광민

Contributors dc:contributor

• 이, 수환
• 대학원 의생명과학과
• 201124156

• Isobavachalcone (IBC)
• Lipopolysacchariode (LPS)
• intercellular adhesion molecule 1 (ICAM-1)
• NF-kB
• cerebrovascular endothelial cells(bEnd.3)
• TLR4 signaling

Language dc:language

ko

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000016127
000000016127

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/10854