J Korean Geriatr Soc.  2007 Sep;11(3):130-138.

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

Affiliations
  • 1Department of Pathology, The Catholic University of Korea, College of Medicine, Seoul, Korea. complt@catholic.ac.kr

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.

Keyword

Alzheimer's disease; NSAIDs; CCL7 chemokine; CXCL2 protein; beta-Secretase

MeSH Terms

Alzheimer Disease
Amyloid Precursor Protein Secretases
Animals
Anti-Inflammatory Agents, Non-Steroidal
Cell Line
Chemokine CCL7
Cytokines
Gene Expression*
Mice*
Microglia
RNA, Messenger
Amyloid Precursor Protein Secretases
Anti-Inflammatory Agents, Non-Steroidal
Chemokine CCL7
Cytokines
RNA, Messenger
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