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Biochem Biophys Res Commun. 2010 Apr 9;394(3):673-8. doi: 10.1016/j.bbrc.2010.03.049. Epub 2010 Mar 11.

The leukotriene B4 receptor, BLT1, is required for the induction of experimental autoimmune encephalomyelitis.

Author information

1
Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. kihara-yasuyuki@umin.net

Abstract

Leukotriene B(4) (LTB(4)) is a potent chemoattractant and activator of neutrophils, macrophages and T cells. These cells are a key component of inflammation and all express BLT1, a high affinity G-protein-coupled receptor for LTB(4). However, little is known about the neuroimmune functions of BLT1. In this study, we describe a distinct role for BLT1 in the pathology of experimental autoimmune encephalomyelitis (EAE) and T(H)1/T(H)17 immune responses. BLT1 mRNA was highly upregulated in the spinal cord of EAE mice, especially during the induction phase. BLT1(-/-) mice had delayed onset and less severe symptoms of EAE than BLT1(+/+) mice. Additionally, inflammatory cells were recruited to the spinal cord of asymptomatic BLT1(+/+), but not BLT1(-/-) mice before the onset of disease. Ex vivo studies showed that both the proliferation and the production of IFN-gamma, TNF-alpha, IL-17 and IL-6 were impaired in BLT1(-/-) cells, as compared with BLT1(+/+) cells. Thus, we suggest that BLT1 exacerbates EAE by regulating the migration of inflammatory cells and T(H)1/T(H)17 immune responses. Our findings provide a novel therapeutic option for the treatment of multiple sclerosis and other T(H)17-mediated diseases.

PMID:
20226760
DOI:
10.1016/j.bbrc.2010.03.049
[Indexed for MEDLINE]

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