help button home button Am J Pathol Epitomics
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
A more recent version of this article appeared on March 1, 2009

Published online before print February 13, 2009
This Article
Right arrow Full Text (Rapid PDF)
Right arrow Supplemental Material
Right arrow All Versions of this Article:
ajpath.2009.080952v1
174/3/898    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Goncalves DaSilva, A.
Right arrow Articles by Yong, V. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Goncalves DaSilva, A.
Right arrow Articles by Yong, V. W.
Copyright © 2009 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2009.080952

Accepted for publication December 2, 2008.

Article

Matrix Metalloproteinase-12 Deficiency Worsens Relapsing-Remitting Experimental Autoimmune Encephalomyelitis in Association with Cytokine and Chemokine Dysregulation

Angelika Goncalves DaSilva and V. Wee Yong@

From the Hotchkiss Brain Institute and Departments of Clinical Neurosciences and Oncology, University of Calgary, Calgary, Canada

@ To whom correspondence should be addressed. E-mail: vyong{at}ucalgary.ca.


  Abstract

The elevation of several members of the matrix metalloproteinase (MMP) family promotes the pathophysiology of both multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Nonetheless, given the multiple activities of MMPs, it remains possible that increased levels of a particular MMP may have beneficial functions during disease progression. We reported previously that MMP-12-/- mice of the 129/SvEv strain had a poorer EAE outcome than wild-type controls. However, we did not determine further differences in disease profiles between these groups. Using the EAE model in 129/SvEv mice, we report that disease in both wild-type and MMP-12-/- mice follows a relapsing-remitting course. Although both mouse groups had similar clinical onsets, subsequent relapses were more severe in MMP-12-/- mice; their residual disability at remission was also higher compared with wild-type controls. The worsened relapses and remissions in MMP-12-/- mice occurred despite a deficiency of the antigen recall capacity of lymph node-derived cells as well as a reduction in the proportion of macrophages in the spinal cord during the chronic phase of EAE. Significantly, large increases of levels of chemokines and cytokines were found in the spinal cords of MMP-12-/- mice during chronic EAE. These results highlight MMP-12 as a beneficial enzyme in EAE and suggest that therapeutic interventions in multiple sclerosis should avoid targeting MMP-12.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2009 by the American Society for Investigative Pathology.