Novel Docosanoids Inhibit Brain Ischemia-Reperfusion-mediated Leukocyte Infiltration and Pro-inflammatory Gene Expression
Author
Marcheselli, Victor L.
Hong, Song
Lukiw, Walter J.
Tian, Xiao Hua
Gronert, Karsten
Musto, Alberto
Hardy, Mattie
Gimenez, Juan M.
Chiang, Nan
Serhan, Charles N.
Bazan, Nicolas G.
Published Version
https://doi.org/10.1074/jbc.M305841200Metadata
Show full item recordCitation
Marcheselli, Victor L., Song Hong, Walter J. Lukiw, Xiao Hua Tian, Karsten Gronert, Alberto Musto, Mattie Hardy, et al. 2003. “Novel Docosanoids Inhibit Brain Ischemia-Reperfusion-Mediated Leukocyte Infiltration and Pro-Inflammatory Gene Expression.” Journal of Biological Chemistry 278 (44): 43807–17. https://doi.org/10.1074/jbc.m305841200.Abstract
Ischemic stroke triggers lipid peroxidation and neuronal injury. Docosahexaenoic acid released from membrane phospholipids during brain ischemia is a major source of lipid peroxides. Leukocyte infiltration and pro-inflammatory gene expression also contribute to stroke damage. In this study using lipidomic analysis, we have identified stereospecific messengers from docosahexaenoate-oxygenation pathways in a mouse stroke model. Aspirin, widely used to prevent cerebrovascular disease, activates an additional pathway, which includes the 17R-resolvins. The newly discovered brain messenger 10,17S-docosatriene potently inhibited leukocyte infiltration, NFkappaB, and cyclooxygenase-2 induction in experimental stroke and elicited neuroprotection. In addition, in neural cells in culture, this lipid messenger also inhibited both interleukin 1-beta-induced NFkappaB activation and cyclooxygenase-2 expression. Thus, the specific novel bioactive docosanoids generated in vivo counteract leukocyte-mediated injury as well as pro-inflammatory gene induction. These results challenge the view that docosahexaenoate only participates in brain damage and demonstrate that this fatty acid is also the endogenous precursor to a neuroprotective signaling response to ischemia-reperfusion.Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:41483534
Collections
- HMS Scholarly Articles [17767]
Contact administrator regarding this item (to report mistakes or request changes)