Induction of the complement component C1qB in brain of transgenic mice with neuronal overexpression of human cyclooxygenase-2.
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.
Spielman
Lauren
L
Neuroinflammation Research Laboratories, Department of Psychiatry, Box 1229, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029, USA.
Winger
David
D
Ho
Lap
L
Aisen
Paul S
PS
Shohami
Esther
E
Pasinetti
Giulio Maria
GM
D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D015922:Complement C1q / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D013449:Sulfonamides; D015922:Complement C1q; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C012655:nimesulide