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Title: Walnut-associated fatty acids inhibit LPS-induced activation of BV-2 microglia

item CAREY, AMANDA - Simmons University
item Fisher, Derek
item BIELINSKI, DONNA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item CAHOON, DANIELLE - Tufts University
item Shukitt-Hale, Barbara

Submitted to: Inflammation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/4/2019
Publication Date: 2/6/2020
Citation: Carey, A.N., Fisher, D.R., Bielinski, D.F., Cahoon, D.S., Shukitt Hale, B. 2020. Walnut-associated fatty acids inhibit LPS-induced activation of BV-2 microglia. Inflammation. 43(1):241-250.

Interpretive Summary: Previous research has shown that pre-treatment of certain brain cells in culture with walnut extract inhibited the cellular response to an inflammatory stressor. In the present study, the effect of treating those brain cells with individual nutrient compounds found in walnuts, omega-3 fatty acids, was assessed. Cells were treated with either of two different omega-3 fatty acids or a combination, prior to or after exposure to the inflammatory stressor. Chemical indicators of inflammation within the cells and those released into the media were measured. Results showed that both fatty acids protected against inflammation when used before exposure to the inflammatory stressor. When the cells were treated with fatty acids after the stressor, inflammation was only partially decreased by fatty acid treatment. The combination of fatty acids was no more effective than either alone. Individual fatty acids may therefore protect nerve cells against inflammation.

Technical Abstract: Background: Walnuts have high levels of the omega-3 fatty acid alpha-linolenic acid (C18:3n-3, ALA) and the omega-6 fatty acid linoleic acid (C18:2n-6, LA). Previous research has demonstrated that pre-treatment of BV-2 microglia, the resident immune cells of the CNS, with walnut extract inhibited lipopolysaccharide (LPS)-induced activation of microglia, as measured by a decrease in oxidative and inflammatory markers. As an extension of that study, the effects of the omega-3 fatty acids on BV-2 microglia were assessed to determine whether they were also effective in reducing stress-mediated signaling in this cell model. Methods: BV-2 murine microglia cells were treated with LA, ALA, or a combination of LA+ALA prior to or after exposure to LPS. Markers of oxidative and inflammatory stress signals, such as nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha), were measured in cell-conditioned media. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression were assessed in cell lysates. Results: Both LA and ALA protected against LPS-induced increases in the stress signals of NO, iNOS, COX-2, and TNF-alpha when used before LPS exposure. When BV-2 microglia were treated with these fatty acids after being treated with LPS, only COX-2 and TNF-alpha were significantly attenuated by the fatty acids. There was no synergism of LA+ALA, as the LA+ALA combination was no more effective than LA or ALA alone, which may indicate that they are working through similar mechanisms. Discussion: Fatty acids, like those found in walnuts, can reduce the release of cytotoxic intermediates and cell signaling molecules from microglia. Therefore, individual fatty acids, such as the ALA and LA found in walnuts and dark-colored fruits, may be effective in reducing inflammatory and OS-mediated signals.