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- Title
Inhibition of calpain attenuates encephalitogenicity of MBP-specific T cells.
- Authors
Guyton, Mary K.; Brahmachari, Saurav; Das, Arabinda; Samantaray, Supriti; Inoue, Jun; Azuma, Mitsuyoshi; Ray, Swapan K.; Banik, Naren L.
- Abstract
Multiple sclerosis (MS) is a T-cell mediated autoimmune disease of the CNS, possessing both immune and neurodegenerative events that lead to disability. Adoptive transfer (AT) of myelin basic protein (MBP)-specific T cells into naïve female SJL/J mice results in a relapsing–remitting (RR) form of experimental autoimmune encephalomyelitis (EAE). Blocking the mechanisms by which MBP-specific T cells are activated before AT may help characterize the immune arm of MS and offer novel targets for therapy. One such target is calpain, which is involved in activation of T cells, migration of immune cells into the CNS, degradation of axonal and myelin proteins, and neuronal apoptosis. Thus, the hypothesis that inhibiting calpain in MBP-specific T cells would diminish their encephalitogenicity in RR-EAE mice was tested. Incubating MBP-specific T cells with the calpain inhibitor SJA6017 before AT markedly suppressed the ability of these T cells to induce clinical symptoms of RR-EAE. These reductions correlated with decreases in demyelination, inflammation, axonal damage, and loss of oligodendrocytes and neurons. Also, calpain : calpastatin ratio, production of truncated Bid, and Bax : Bcl-2 ratio, and activities of calpain and caspases, and internucleosomal DNA fragmentation were attenuated. Thus, these data suggest calpain as a promising target for treating EAE and MS.
- Subjects
MULTIPLE sclerosis; CALPAIN; CENTRAL nervous system; T cells; MYELIN basic protein
- Publication
Journal of Neurochemistry, 2009, Vol 110, Issue 6, p1895
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2009.06287.x