Affiliations: [a] Department of Anatomy, University of Mississippi Medical Center, 2500 N. State St., Jackson, MS 39216, USA | [b] ENH Research Institute, Department of Medicine, 1001 University Place, Evanston, IL 60201, USA | [c] Department of Preventive Medicine, University of Mississippi Medical Center, 2500 N. State St., Jackson, MS 39216, USA | [d] Department of Neurology, Henry Ford Health Sciences Center, Detroit, MI 48202, USA
Correspondence:
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Corresponding author: March D. Ard, Ph.D., Dept. of Anatomy, Univ. of Mississippi Med. Ctr., 2500 N. State St., Jackson, MS 39216, USA. Tel.: +1 601 984 1645; Fax: +1 601 984 1655; E-mail: [email protected].
Abstract: 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-1β (IL-1β), and other inflammatory mediators. Apolipoprotein E isoform 4 (apoE4), coded for by the gene APOE4 (ε4), 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-1β 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-1β. The increase in PGE2 release stimulated by apoE4 was not accompanied by the upregulation of the COX-2 enzyme in microglia.
