Affiliation:
1. Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo, Japan
2. Department of Biochemistry, Juntendo University Graduate School of Medicine, Hongo, Bunkyo-ku, Tokyo, Japan
Abstract
Abstract
Leukotrienes (LTs) are inflammatory mediators derived from arachidonic acid. LTs include the di-hydroxy acid LT (LTB4) and the cysteinyl LTs (CysLTs; LTC4, LTD4 and LTE4), all of which are involved in both acute and chronic inflammation. We and other groups identified a high-affinity LTB4 receptor, BLT1; the LTC4 and LTD4 receptors, CysLT1 and CysLT2; and the LTE4 receptor, GPR99. Pharmacological studies have shown that BLT1 signaling stimulates degranulation, chemotaxis and phagocytosis of neutrophils, whereas CysLT1 and CysLT2 signaling induces airway inflammation by increasing vascular permeability and the contraction of bronchial smooth muscle. Recently, we and other groups suggested that the LTB4–BLT1 axis and the cysteinyl LTs–CysLT1/2 axis are involved in chronic inflammatory diseases including asthma, atopic dermatitis, psoriasis, atherosclerosis, arthritis, obesity, cancer and age-related macular degeneration using animal models for disease and gene knockout mice. This review describes the classical and novel functions of LTs and their receptors in several inflammatory diseases and discusses the potential clinical applications of antagonists for LT receptors and inhibitors of LT biosynthesis.
Funder
Ministry of Education, Culture, Sports, Science, and Technology
Japan Society for the Promotion of Science
Naito Foundation
Ono Medical Research Foundation
Uehara Memorial Foundation
Mitsubishi Foundation
Takeda Science Foundation
Foundation for Strategic Research Projects in Private Universities of the MEXT
Institute for Environmental and Gender-Specific Medicine
Publisher
Oxford University Press (OUP)
Subject
Immunology,General Medicine,Immunology and Allergy
Cited by
65 articles.
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