Abstract
We report that overexpression of human (h) cyclooxygenase-2 h(COX-2) in the brain of a transgenic mouse line leads to selective induction of endogenous complement component C1qB expression in neurons. No detectable induction of the C3 and C4 complement components in the brain was found. Chronic treatment of mice with the selective COX-2 inhibitor nimesulide reduced the hCOX-2-mediated induction of hippocampal C1qB mRNA expression. The data suggest that neuronal COX-2 expression may influence inflammatory responses in the brain, in part through modulation of complement gene expression. Because there is extensive evidence that C1q and other complement components are involved in Alzheimer's disease (AD) neurodegeneration, this study advances our understanding of the apparent benefits of COX-2 inhibition in AD.
MeSH terms
-
Alzheimer Disease / genetics*
-
Alzheimer Disease / physiopathology
-
Animals
-
Brain / drug effects*
-
Brain / physiopathology
-
Complement C1q / drug effects*
-
Complement C1q / genetics*
-
Complement C1q / physiology
-
Cyclooxygenase 2
-
Cyclooxygenase 2 Inhibitors
-
Cyclooxygenase Inhibitors / pharmacology
-
Gene Expression / drug effects*
-
Gene Expression / genetics
-
Gene Expression / physiology
-
Gene Expression Regulation / drug effects*
-
Gene Expression Regulation / genetics
-
Gene Expression Regulation / physiology
-
Humans
-
Isoenzymes / drug effects*
-
Isoenzymes / genetics*
-
Isoenzymes / physiology
-
Male
-
Membrane Proteins
-
Mice
-
Mice, Transgenic
-
Neurons / drug effects*
-
Neurons / physiology
-
Prostaglandin-Endoperoxide Synthases / drug effects*
-
Prostaglandin-Endoperoxide Synthases / genetics*
-
Prostaglandin-Endoperoxide Synthases / physiology
-
Sulfonamides / pharmacology
Substances
-
Cyclooxygenase 2 Inhibitors
-
Cyclooxygenase Inhibitors
-
Isoenzymes
-
Membrane Proteins
-
Sulfonamides
-
Complement C1q
-
Cyclooxygenase 2
-
PTGS2 protein, human
-
Prostaglandin-Endoperoxide Synthases
-
nimesulide