This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Hebb, A. Articles by Robertson, G. Search for Related Content PubMed PubMed Citation Articles by Hebb, A. Articles by Robertson, G. Social Bookmarking                         What's this?

Expression of the inhibitor of apoptosis protein family in multiple sclerosis reveals a potential immunomodulatory role during autoimmune mediated demyelination

Department of Pharmacology, Dalhousie University, Halifax, NS, B3H 1X5, Canada

CS Moore

Department of Pharmacology, Dalhousie University, Halifax, NS, B3H 1X5, Canada

V Bhan

Department of Medicine (Neurology), Dalhousie University, Halifax, NS, B3H 1V7, Canada

T Campbell

Department of Medicine (Neurology), Dalhousie University, Halifax, NS, B3H 1V7, Canada

JD Fisk

Department of Psychiatry, Dalhousie University, Halifax, NS, B3H 2E2, Canada; Department of Psychology, QEII Health Sciences Centre, Halifax, NS, B3H 2E2, Canada

HA Robertson

Department of Pharmacology, Dalhousie University, Halifax, NS, B3H 1X5, Canada

M Thorne

Department of Pharmacology, Dalhousie University, Halifax, NS, B3H 1X5, Canada

E Lacasse

Aegera Therapeutics Inc., Nun’s Island (Montreal), PQ, H3E 1A8, Canada

M Holcik

Apoptosis Research Centre, Children's Hospital of Eastern Ontario, Ottawa, Ontario, KIH 8L1, Canada

J Gillard

Aegera Therapeutics Inc., Nun’s Island (Montreal), PQ, H3E 1A8, Canada

SJ Crocker

Molecular and Integrative Neuroscience Department, the Scripps Research Institute, La Jolla, CA, 92037, USA

GS Robertson

Department of Pharmacology, Dalhousie University, Halifax, NS, B3H 1X5, Canada; Department of Psychiatry, Dalhousie University, Halifax, NS, B3H 2E2, Canada

A failure of autoreactive T cells to undergo apoptosis may contribute to the pathogenesis of multiple sclerosis (MS). The role of the inhibitor of apoptosis (IAP) family of anti-apoptotic proteins such as X-linked IAP (XIAP), human inhibitor of apoptosis-1 (HIAP-1), human inhibitor of apoptosis-2 (HIAP-2), neuronal apoptosis inhibitory protein (NAIP) and Survivin in relapsing–remitting, secondary-progressive, primary-progressive or benign forms of MS is unclear. We report here that expression of the IAP family of genes in peripheral blood samples and brain tissues from MS cases support a role for differential regulation of these potent anti-apoptotic proteins in the pathology of MS. XIAP mRNA and protein levels were elevated in peripheral blood mononuclear cells from patients with active disease relative to normal subjects. In patients with active MS, HIAP-1 and HIAP-2 mRNA levels were elevated in resting T cells while NAIP mRNA was increased in whole blood. In post-mortem MS brain tissue, XIAP and HIAP-1 in myelin lesions were co-localized with microglia and T cells, respectively. Only in primary-progressive patients was Survivin expression elevated suggestive of a distinct pathological basis for this subtype of MS. Taken together, these results suggest that patterns of inhibitor of apoptosis expression in immune cells may have value in distinguishing between MS subtypes and offer insight into the mechanisms responsible for their distinct clinical courses.

Key Words: brain • CD3+ cells • demyelination • lesions • microglia

Multiple Sclerosis, Vol. 14, No. 5, 577-594 (2008)
DOI: 10.1177/1352458507087468


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?