The role of α4 integrin in Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease: an infectious animal model for multiple sclerosis (MS)

Natalizumab, which is an antibody against α4 integrin, has been used for the treatment of multiple sclerosis. In the present study, we investigated both the role of α4 integrin and the therapeutic effect of HCA3551, a newly synthesized orally active small molecule α4 integrin antagonist, in the deve...

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Bibliographic Details
Published in:International Immunology 2016-12, Vol.28 (12), p.575-584
Main Authors: Hirano, Yuta, Kobayashi, Kunitoshi, Tomiki, Hiroki, Inaba, Yuhji, Ichikawa, Motoki, Kim, Byung S, Koh, Chang-Sung
Format: Article
Language:English
Subjects:
Animals
Demyelinating Diseases - metabolism
Demyelinating Diseases - virology
Disease Models, Animal
Female
Integrin alpha4 - genetics
Integrin alpha4 - immunology
Integrin alpha4 - metabolism
Mice
Mice, Inbred Strains
Multiple Sclerosis - metabolism
Multiple Sclerosis - virology
Original Research
Theilovirus - pathogenicity
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Summary:Natalizumab, which is an antibody against α4 integrin, has been used for the treatment of multiple sclerosis. In the present study, we investigated both the role of α4 integrin and the therapeutic effect of HCA3551, a newly synthesized orally active small molecule α4 integrin antagonist, in the development of Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). The mRNA levels of α4 integrins were significantly up-regulated in the central nervous system (CNS) of mice with TMEV-IDD as compared with naive mice (*P < 0.05). HCA3551 treatment in the effector phase significantly suppressed both the clinical and histological development of TMEV-IDD. The number of infiltrating mononuclear inflammatory cells in the CNS was significantly decreased in the mice treated with HCA3551 (**P < 0.01). The labeling indices for CD68 antigen and the absolute cell numbers of TNF-α-producing CD4 T cells and IFN-γ-producing CD8 T cells were significantly decreased in the CNS of mice treated with HCA3551 (*P < 0.05). HCA3551 treatment in the effector phase might inhibit the binding of α4 integrin to vascular cell adhesion molecule-1, thereby decreasing the number of mononuclear cells in the CNS.
ISSN:0953-8178
1460-2377
DOI:10.1093/intimm/dxw045