Inhibition of calpain attenuates encephalitogenicity of MBP-specific T cells

Mary K. Guyton, Saurav Brahmachari, Arabinda Das, Supriti Samantaray, Jun Inoue, Mitsuyoshi Azuma, Swapan K. Ray, Naren L. Banik

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1895-1907
Number of pages13
JournalJournal of Neurochemistry
Volume110
Issue number6
DOIs
StatePublished - Sep 2009
Externally publishedYes

Keywords

  • Apoptosis
  • Encephalitogenicity
  • Experimental autoimmune encephalomyelitis
  • Inflammation
  • Myelin basic protein-specific T cells

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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