A turn on and a turn off: BLT1 and BLT2 mechanisms in the lung

Abstract

Leukotriene B₄ (LTB₄), a potent lipid mediator of inflammation derived from arachidonic acid through the action of 5-lipoxygenase, has been implicated in the pathophysiology of several inflammatory diseases, including asthma and chronic obstructive pulmonary disease. A high-affinity LTB₄ receptor BLT1 has been shown to exert proinflammatory roles. A cyclooxygenase metabolite, 12(S)-hydroxyheptadeca-5Z, 8E, 10E-trienoic acid (12-HHT), is an endogenous ligand for BLT2, a low-affinity LTB₄ receptor. The recent study indicated that BLT2 has a protective role in allergic airway inflammation, suggesting different functions between BLT1 and BLT2 in the pathogenesis of asthma. Selective BLT1 antagonists may have a potential therapeutic application in patients with asthma, and BLT2 may represent a novel therapeutic target for lung diseases.

Keywords::

• BLT1
• BLT2
• LTB₄
• lung disease

Acknowledgements

The authors thank Takehiko Yokomizo for critical reading and comments.

Financial & competing interests disclosure

This work was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (25293192, 24591172). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.