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[P3–124]: DIETARY LINOLEIC ACID DIFFERENTIALLY INFLUENCES BRAIN FADS ACTIVITIES INCREASING AN N‐6 METABOLITE THAT INHIBITS INFLAMMATION AND PROMOTES AMYLOID‐β CLEARANCE
Author(s) -
Cole Gregory M.,
Ma QiuLan,
Teter Bruce,
Jones Mychica,
Frautschy Sally A.
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.1335
Subject(s) - docosapentaenoic acid , polyunsaturated fatty acid , arachidonic acid , inflammation , linoleic acid , lipoxygenase , proinflammatory cytokine , metabolite , eicosanoid , fads2 , cognitive decline , apolipoprotein e , endocrinology , biochemistry , chemistry , biology , docosahexaenoic acid , fatty acid , medicine , enzyme , immunology , disease , dementia
Background: Alzheimer’s disease (AD) is a neurodegenerative disease associated with the deposition of extracellular (Aß) plaques within the brain and neuroinflammation. The NLRP3 inflammasome, in particular, is activated in AD. This results in the downstream production of the proinflammatory cytokines IL1ß and IL18, a reduced generation of the anti-inflammatory IL33 cytokine, and the impairment of Ab-phagocytosis. Herein we analyzed possible correlations between inflammasome activation and Ab-phagocytosis in an in vitro system. Methods: Existing flow cytometry methods that lack image-based analysis capabilities fail to fully discriminate between adherent or cells-internalized Aß; the AMNIS technology can perform simultaneous detection of Aß-phagocytosis in different in vitro conditions. THP-1 cells differentiated into macrophages by PMA were stimulated with LPS (1ug/ml for 24 hours)+ Aß (1ug/ml for 1 hour), or with LPS+ Aß+ the NLRP3 activators Nigericin (5uM for 1 hour) or only with Aß (1ug/ml for 1 hour) in the presence/absence of IL33 (10ng/ml for 18 hours). Phagocitosis was measured as the ratio between intra and extra cellular FITC-conjugated Aß; cytokine production was measured by ELISA. Results: A significant increase in IL1ß production (p1⁄40.001) and a drastic reduction of Ab-phagocytosis (p1⁄40.0001) were seen when cells stimulated by LPS+ Ab+Nigericin were compare to those stimulated by LPS+Aß or Aß alone. Notably, IL1ß production was drastically reduced and Aßphagocytosis was significantly increased (both p1⁄40.001) in LPS+ Aß+Nigericin-stimulated cells in the presence of IL33. Conclusions: IL33 reduces inflammasome-associated inflammation and improves macrophage-mediated Aß-phagocytosis. These results allow the speculation that this cytokine could be beneficial in the therapy of AD.