Poly(ADP-ribose) polymerase 2 contributes to neuroinflammation and neurological dysfunction in mouse experimental autoimmune encephalomyelitis

Journal of Neuroinflammation

Christopher M Anderson²  Gilbert de Murcia³  Tiina M Kauppinen¹  Brian A Dolhun²  Jillian L Stobart²  Michael B Cossoy⁴  Ping Lu²  Amit Kamboj² 

[1] Department of Pharmacology and Therapeutics, University of Manitoba and Division of Neurodegenerative Disorders, St Boniface Hospital Research, Winnipeg, Canada;Division of Neurodegenerative Disorders, St Boniface Hospital Research, Winnipeg, Canada;Department ‘Intégrité du Génome’ de l’UMR 7175, École Supérieure de Biotechnologie de Strasbourg, Illkirch Cedex, France;Department of Internal Medicine, University of Manitoba, Winnipeg, Canada

关键词: Th17;    Th1;    PARP-2;    PARP-1;    Multiple sclerosis;    Neuroinflammation;    Experimental autoimmune encephalomyelitis;    Demyelination;    CD11b;    CD4;   

Others  :  1159997
DOI  :  10.1186/1742-2094-10-49

 received in 2012-10-16, accepted in 2013-04-10,  发布年份 2013

【 摘 要 】

Background

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis characterized by entry of activated T cells and antigen presenting cells into the central nervous system and subsequent autoimmune destruction of nerve myelin. Previous studies revealed that non-selective inhibition of poly(ADP-ribose) polymerases (PARPs) 1 and 2 protect against neuroinflammation and motor dysfunction associated with EAE, but the role of the PARP-2 isoform has not yet been investigated selectively.

Results

EAE was induced in mice lacking PARP-2, and neurological EAE signs, blood-spine barrier (BSB) permeability, demyelination and inflammatory infiltration were monitored for 35 days after immunization. Mice lacking PARP-2 exhibited significantly reduced overall disease burden and peak neurological dysfunction. PARP-2 deletion also significantly delayed EAE onset and reduced BSB permeability, demyelination and central nervous system (CNS) markers of proinflammatory Th1 and Th17 T helper lymphocytes.

Conclusions

This study represents the first description of a significant role for PARP-2 in neuroinflammation and neurological dysfunction in EAE.

【 授权许可】

   
2013 Kamboj et al.; licensee BioMed Central Ltd.

【 图 表 】

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