Experimental allergic encephalomyelitis is exacerbated in mice deficient for 12/15-lipoxygenase or 5-lipoxygenase.
12/15-Lipoxygenase (12/15-LO) produces 15-hydroxyeicosatetraenoic acid (15-HETE) and 13-hydroxyoctadecadienoic acid (13-HODE) which are agonists for peroxisome proliferator-activated receptor-gamma (PPARgamma). PPARgamma agonists reduce clinical severity of experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis. In contrast, 5-lipoxygenase (5-LO) produces the generally proinflammatory leukotrienes (LTs) which would be expected to worsen EAE. We tested the hypotheses that EAE severity would be exacerbated in 12/15-LO-deficient mice and attenuated in 5-LO-deficient mice. 12/15-LO deficiency conferred a significantly worse disease course, and surprisingly, 5-LO deficiency also caused significantly more severe EAE compared to control mice. These data suggest that PPARgamma-regulated gene expression and that 5-LO production of certain LTs have the ability to diminish EAE. Continued analysis will provide insight into the endogenous LO-generated effectors that assist in tempering EAE.
Emerson
Mitchell R
MR
Department of Molecular and Integrative Physiology, Ralph L. Smith Mental Retardation Research Center, University of Kansas Medical Center, Kansas City, KS 66160, USA. memers@midwestern.edu
LeVine
Steven M
SM
D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics*; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics*; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000503:physiopathology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009103:Multiple Sclerosis / Q000378:metabolism / Q000503:physiopathology; D012720:Severity of Illness Index
C475064:12-15-lipoxygenase; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase