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KMID : 0828520070110030130
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Journal of the Korean Geriatrics Society
2007 Volume.11 No. 3 p.130 ~ p.138
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Non-Steroidal Anti-Inflammatory Drugs Change Various Inflammatory Mediator-Related Gene Expression In Abeta1-42 Activated Mouse Microglial Cell
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Choi Young-Sook
Kim Sang-Ho
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Abstract
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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.
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KEYWORD
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Alzheimers disease, NSAIDs, CCL7 chemokine, CXCL2 protein, beta-Secretase
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