Experimental Allergic Encephalomyelitis Is Exacerbated in Mice Deficient for 12/15-lipoxygenase or 5-lipoxygenase

Brain Res. 2004 Sep 17;1021(1):140-5. doi: 10.1016/j.brainres.2004.06.045.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arachidonate 12-Lipoxygenase / genetics*
  • Arachidonate 15-Lipoxygenase / genetics*
  • Arachidonate 5-Lipoxygenase / genetics*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism*
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology*
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Multiple Sclerosis / metabolism
  • Multiple Sclerosis / physiopathology
  • Severity of Illness Index

Substances

  • 12-15-lipoxygenase
  • Arachidonate 12-Lipoxygenase
  • Arachidonate 15-Lipoxygenase
  • Arachidonate 5-Lipoxygenase