The role of prostaglandins in allergic lung inflammation and asthma

Abstract

Prostaglandins (PGs) are products of the COX pathway of arachidonic acid metabolism. There are five primary PGs, PGD₂, PGE₂, PGF₂, PGI₂ and thromboxane A₂, all of which signal through distinct seven transmembrane, G-protein coupled receptors. Some PGs may counteract the actions of others, or even the same PG may have opposing physiologic or immunologic effects, depending on the specific receptor through which it signals. In this review, we examine the effects of COX activity and the various PGs on allergic airway inflammation and physiology that is associated with asthma. We also highlight the potential therapeutic benefit of targeting PGs in allergic lung inflammation and asthma based on basic science, animal model and human studies.

Keywords:

• allergy
• asthma
• COX
• inflammation
• prostaglandin

Financial & competing interests disclosure

This work was supported by NIH Grants R01 AI 111820, U19 AI 095227-02, R01 HL 090664-04 and Veteran Affairs Grant 2I01BX000624. 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.

Key issues

• COX inhibition, either by gene deletion or pharmacologic approach, augmented allergic inflammation in several animal models.

• Prostaglandin (PG)D₂ is the major mast cell-derived prostanoid and is elaborated in nanogram quantities in these cells in response to IgE-mediated activation.

• Mouse studies suggest that signaling through D prostanoid augments allergic inflammation and a D prostanoid 2 antagonist significantly improved both quality of life and night time symptom score in a randomized, double-blind, placebo-controlled trial in humans with moderate-persistent asthma.

• PGE₂ inhibits the cysteinyl leukotriene synthesis pathway and inhibition of PGE₂ synthesis is a major pathogenic mechanism of aspirin-exacerbated respiratory disease.

• PGI₂ restrains allergic airway inflammation in mice by inhibiting dendritic cell activation of CD4⁺ Th2 cells, Th2 cell differentiation and eosinophil migration.

• Thromboxane A₂ is an inflammatory and bronchoconstrictive mediator in asthma.

• PGF_2α is a pro-fibrotic mediator in pulmonary fibrosis.

• Future research will continue to expand understanding of the molecular signaling pathways of prostaglandins and further identify therapeutic options in pulmonary disease.

Notes