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Inhibition of calpain attenuates encephalitogenicity of MBP‐specific T cells
Author(s) -
Guyton Mary K.,
Brahmachari Saurav,
Das Arabinda,
Samantaray Supriti,
Inoue Jun,
Azuma Mitsuyoshi,
Ray Swapan K.,
Banik Naren L.
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06287.x
Subject(s) - calpain , experimental autoimmune encephalomyelitis , myelin basic protein , multiple sclerosis , adoptive cell transfer , myelin , immune system , apoptosis , biology , microbiology and biotechnology , immunology , calpastatin , inflammation , t cell , chemistry , central nervous system , neuroscience , biochemistry , enzyme
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.