Non-Steroidal Anti-Inflammatory Drugs Change Various Inflammatory Mediator-Related Gene Expression In Abeta1-42 Activated Mouse Microglial Cell

Choi, Young Sook; Kim, Sang Ho

Original Article

Journal of the Korean Geriatrics Society 2007;11(3):130-138.
Published online September 30, 2007.

Non-Steroidal Anti-Inflammatory Drugs Change Various Inflammatory Mediator-Related Gene Expression In Abeta1-42 Activated Mouse Microglial Cell

Young Sook Choi, Sang Ho Kim

Department of Pathology, The Catholic University of Korea, College of Medicine, Seoul, Korea. complt@catholic.ac.kr

아밀로이드베타단백 투여 후 활성화된 마우스 소교세포에 Non-Steroidal Anti-Inflammatory Drugs 투여로 염증매개물 관련 유전자들의 변화

Abstract

BACKGROUND
We investigated whether non-steroidal anti-inflammatory drugs(NSAIDs) could influence the expression of a few inflammatory mediator-related genes in amyloid-beta1-42(Abeta42)-activated microglia.
METHODS
BV-2 cells, a murine microglial cell line, were pretreated with a single dose of 20microM of aggregated Abeta42 for 18 hours followed by incubation with ibuprofen(100microM), indomethacin(150microM) or ketorolac(10nM) for 24 hours. Expression of mRNAs for CCL7(beta-chemokine), CXCL2(alpha-chemokine), CCR7(beta-chemokine receptor), interleukin(IL)-1alpha, matrix metalloproteinase(MMP)-3, beta-secretase(BACE1) and cyclooxygenase(COX)-2 gene were measured with quantitative realtime reverse transcriptase(RT)-PCR.
RESULTS
Abeta42 increased expression of mRNAs for CCL7, CXCL2, CCR7, IL-1alpha, MMP-3, BACE1 and COX-2 genes. Administration of each NSAIDs effectively lowered the expression of these genes in Abeta42-activated microglia.
CONCLUSION
NSAIDs inhibit increased expression of a few cytokines, chemokine receptor and inflammatory mediatorrelated protease genes in Abeta42-activated microglia. These data demonstrate a possible mechanism how NSAIDS may decrease the risk and delay the onset of chronic neuroinflammatory process in AD.

Key Words: Alzheimer's disease, NSAIDs, CCL7 chemokine, CXCL2 protein, beta-Secretase

초 록

연구배경: Aβ42 투여로 활성화된 마우스 소교세포에서 염증매개물 관련 유전자들의 발현 증가를 확인 후 NSAIDs 투여로 그 발현억제 여부를 보고자 하였다.

방법: 마우스 소교세포주 BV-2에 20μM의 aggregated Aβ42를 투여하여 18시간 배양 후 이어서 ibuprofen(100μM), indomethacin(150μM), ketorolac(10 nM)을 각각 투여하여 24시간 배양하였다. CCL7(β-chemokine), CXCL2(α-chemokine), CCR7(β-chemokine receptor), IL-1α, MMP-3, β-secretase(BACE1), COX-2 유전자의 mRNA 발현 증감을 정량적 실시간 역전사중합효소 반응법으로 측정하여 대조군과 비교하였다.

결과: Aβ42는 소교세포를 활성화시켜 7가지 표적유전자 모두의 발현을 증가시켰고, 이어서 투여된 3가지 NSAIDs 모두 이들의 발현을 각각 의의있게 억제하였다.

결론: NSAIDs는 Aβ42에 의하여 활성화된 소교세포로부터 발현이 증가된 염증관련 몇 가지 시토카인, chemokine 수용체 및 염증매개물 관련 효소 유전자들을 모두 억제시켰다.