Uncoupling protein 2 has protective function during experimental autoimmune encephalomyelitis.
Uncoupling protein 2 (UCP2) is a member of the mitochondrial transporter superfamily that is expressed in many tissues, including immune cells. UCP2 prevents oxidative stress by reducing reactive oxygen species. Using UCP2-deficient mice, it was shown that UCP2 is involved in the regulation of insulin secretion, in the resistance to infection, and in atherosclerosis. Here, we investigated the role of UCP2 in experimental autoimmune encephalomyelitis, a murine model of multiple sclerosis. Immunized C57BL/6J UCP2-deficient mice showed a slightly delayed onset during experimental autoimmune encephalomyelitis (13.0 +/- 0.6 versus 11.5 +/- 0.8 in wild-type controls) and developed significantly higher disease scores than littermate controls (maximum disease score of 2.9 +/- 0.2 versus 1.7 +/- 0.2, P = 0.001). Higher levels of infiltrating T cells into the spinal cord meninges and parenchyma were observed. The T-cell proliferative response to the specific antigen was increased in UCP2-deficient mice compared with littermate controls, and CD4 cells of UCP2 knockout mice produced significantly higher levels of pro-inflammatory cytokines, eg, tumor necrosis factor-alpha and interleukin-2, resulting from a Th1 response. Mice lacking UCP2 also developed a higher B-cell response. Concomitantly, CD4 and CD8 cells of the UCP2-deficient mice showed increased production of reactive oxygen species. These results suggest a protective function of UCP2 in chronic inflammatory diseases such as multiple sclerosis.
Vogler
Susanne
S
Department of Immunology, University of Rostock, Germany.
Pahnke
Jens
J
Rousset
Sophie
S
Ricquier
Daniel
D
Moch
Holger
H
Miroux
Bruno
B
Ibrahim
Saleh M
SM
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000517:prevention & control; D006023:Glycoproteins / Q000494:pharmacology; D007111:Immunity, Cellular; D007114:Immunization; D007473:Ion Channels; D008198:Lymph Nodes / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D063308:Myelin-Oligodendrocyte Glycoprotein; D009928:Organ Specificity; D010446:Peptide Fragments / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism*; D013997:Time Factors; D000071246:Uncoupling Protein 2
D006023:Glycoproteins; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; C445081:myelin oligodendrocyte glycoprotein (35-55)