Deletion of UCP2 in iNOS deficient mice reduces the severity of the disease during experimental autoimmune encephalomyelitis

PLoS One. 2011;6(8):e22841. doi: 10.1371/journal.pone.0022841. Epub 2011 Aug 8.

Abstract

Uncoupling protein 2 is a member of the mitochondrial anion carrier family that is widely expressed in neurons and the immune cells of humans. Deletion of Ucp2 gene in mice pre-activates the immune system leading to higher resistance toward infection and to an increased susceptibility to develop chronic inflammatory diseases as previously exemplified with the Experimental Autoimmune Encephalomyelitis (EAE), a mouse model for multiple sclerosis. Given that oxidative stress is enhanced in Ucp2-/- mice and that nitric oxide (NO) also plays a critical function in redox balance and in chronic inflammation, we generated mice deficient for both Ucp2 and iNos genes and submitted them to EAE. Mice lacking iNos gene exhibited the highest clinical score (3.4+/-0.5 p<0.05). Surprisingly, mice deficient for both genes developed milder disease with reduced immune cell infiltration, cytokines and ROS production as compared to iNos-/- mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / pathology
  • Cytokines / genetics
  • Cytokines / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / genetics*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Glutathione / metabolism
  • Glutathione Disulfide / metabolism
  • Humans
  • Immune System / metabolism
  • Immune System / pathology
  • Ion Channels / deficiency
  • Ion Channels / genetics*
  • Macrophages, Peritoneal / metabolism
  • Macrophages, Peritoneal / pathology
  • Mice
  • Mice, Knockout
  • Mitochondrial Proteins / deficiency
  • Mitochondrial Proteins / genetics*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / deficiency
  • Nitric Oxide Synthase Type II / genetics*
  • Oxidation-Reduction
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Severity of Illness Index
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Uncoupling Protein 2

Substances

  • Cytokines
  • Ion Channels
  • Mitochondrial Proteins
  • Reactive Oxygen Species
  • UCP2 protein, human
  • Ucp2 protein, mouse
  • Uncoupling Protein 2
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Glutathione
  • Glutathione Disulfide