Isoform-specific effects of apolipoprotein E on secretion of inflammatory mediators in adult rat microglia.
Inflammation mediated by activated microglia cells has been shown to contribute to the pathogenesis of Alzheimer disease (AD) [1]. Microglia are the immune cells in the central nervous system, and when activated they secrete the lipid-derived mediator prostaglandin E2 (PGE2), the cytokine interleukin-1beta (IL-1beta), and other inflammatory mediators. Apolipoprotein E isoform 4 (apoE4), coded for by the gene APOE4 (epsilon4), has been shown to correlate with higher risk of onset of AD, as well as with increased severity of other diseases with a neuroinflammatory component. This study investigated isoform-specific effects of apoE on the regulation of PGE2, COX2, and IL-1beta expression. Two physiologically relevant preparations of apoE displayed an isoform-specific effect on inflammation in primary adult microglia cultured from adult rat brain cortex. Specifically, apoE4 alone, but not the more common isoform apoE3, stimulated secretion of PGE2 and IL-1beta. The increase in PGE2 release stimulated by apoE4 was not accompanied by the upregulation of the COX-2 enzyme in microglia.
Chen
Shuang
S
Department of Anatomy, University of Mississippi Medical Center, 2500 N. State St., Jackson, MS 39216, USA.
Averett
Natale T
NT
Manelli
Arlene
A
Ladu
Mary Jo
MJ
May
Warren
W
Ard
March D
MD
D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology*; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis*; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology*; D007375:Interleukin-1 / Q000096:biosynthesis*; D017628:Microglia / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D020033:Protein Isoforms / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001057:Apolipoproteins E; D007375:Interleukin-1; D020033:Protein Isoforms; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone