Current state and future prospect of the therapeutic strategy targeting cysteinyl leukotriene metabolism in asthma

Takayuki Yamamoto, Jun Miyata, Makoto Arita, Koichi Fukunaga, Akihiko Kawana

Research output: Contribution to journalReview article

Abstract

Asthma is an allergic disorder with dominant type 2 airway inflammation, and its prevalence is increasing worldwide. Inhalation of corticosteroids is the primary treatment for asthma along with add-on drugs, including long-acting β2 agonists and/or cysteinyl leukotriene (cys-LT) receptor antagonists, in patients with poorly controlled asthma. Cys-LTs are composed of leukotriene C4 (LTC4), LTD4, and LTE4, which are enzymatically metabolized from arachidonic acid. These molecules act as inflammatory mediators through different types of high-affinity receptors, namely, CysLT1, CysLT2, and CysLT3 (also named as GPR99). CysLT1 antagonists possessing anti-inflammatory and bronchodilatory effects can be orally administered to patients with asthma. Recently, molecular biology-based studies have revealed the mechanism of inflammatory responses via other receptors, such as CysLT2 and CysLT3, as well as the importance of upstream inflammatory regulators, including type 2 cytokines (e.g., interleukins 4 and 5), in controlling cys-LT metabolism. These findings indicate the therapeutic potential of pharmacological agents targeting cys-LT metabolism-related receptors and enzymes, and antibody drugs neutralizing or antagonizing type 2 cytokines. This review focuses on the current state and future prospect of the therapeutic strategy targeting cys-LT metabolism.

Original languageEnglish
Pages (from-to)534-543
Number of pages10
JournalRespiratory Investigation
Volume57
Issue number6
DOIs
Publication statusPublished - 2019 Nov

Fingerprint

Asthma
Leukotriene E4
Cytokines
Leukotriene D4
Leukotriene Antagonists
Leukotriene C4
Interleukin-5
Therapeutics
Neutralizing Antibodies
Arachidonic Acid
Interleukin-4
Pharmaceutical Preparations
Inhalation
Molecular Biology
Adrenal Cortex Hormones
Anti-Inflammatory Agents
Pharmacology
Inflammation
cysteinyl-leukotriene
Enzymes

Keywords

  • Antibodies
  • Asthma
  • Cysteinyl leukotrienes
  • Leukotriene receptor antagonist
  • Type 2 cytokines

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Current state and future prospect of the therapeutic strategy targeting cysteinyl leukotriene metabolism in asthma. / Yamamoto, Takayuki; Miyata, Jun; Arita, Makoto; Fukunaga, Koichi; Kawana, Akihiko.

In: Respiratory Investigation, Vol. 57, No. 6, 11.2019, p. 534-543.

Research output: Contribution to journalReview article

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