Two distinct leukotriene B4 receptors, BLT1 and BLT2.

Abstract:

:Leukotriene B4 (LTB4) is a potent inflammatory mediator derived from arachidonic acid. Two G protein-coupled receptors for LTB4 have been identified: a high-affinity receptor, BLT1, and a low-affinity receptor, BLT2. Both receptors mainly couple to pertussis toxin-sensitive Gi-like G proteins and induce cell migration. 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (12-HHT) was identified to bind BLT2 with higher affinity than LTB4. Expression of BLT1 was confirmed in type 1 helper T cells, type 2 helper T cells, type 17 helper T cells, effector CD8(+) T cells, dendritic cells and osteoclasts in addition to granulocytes, eosinophils and macrophages, and BLT1-deficient mice showed greatly reduced phenotypes in models of various inflammatory diseases, such as peritonitis, bronchial asthma, rheumatoid arthritis, atherosclerosis and osteoporosis. In mice, BLT2 expression is restricted to intestinal epithelial cells and epidermal keratinocytes. BLT2-deficient mice showed enhanced colitis after administration of dextran sulfate, possibly due to reduced intestinal barrier function. An aspirin-dependent reduction in 12-HHT production was responsible for delayed skin wound healing, showing that the 12-HHT/BLT2 axis also plays an important role in skin biology. BLT1 and BLT2 are therefore potential targets for the development of novel drugs.

journal_name

J Biochem

journal_title

Journal of biochemistry

authors

Yokomizo T

doi

10.1093/jb/mvu078

subject

Has Abstract

pub_date

2015-02-01 00:00:00

pages

65-71

issue

2

eissn

0021-924X

issn

1756-2651

pii

mvu078

journal_volume

157

pub_type

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