Prostaglandins in asthma and allergic diseases

Abstract

Prostaglandins are synthesized through the metabolism of arachidonic acid via the cyclooxygenase pathway. There are five primary prostaglandins, PGD₂, PGE₂, PGF₂, PGI₂, and thromboxane B₂, that all signal through distinct seven transmembrane, G-protein coupled receptors. The receptors through which the prostaglandins signal determines their immunologic or physiologic effects. For instance, the same prostaglandin may have opposing properties, dependent upon the signaling pathways activated. In this article, we will detail how inhibition of cyclooxygenase metabolism and regulation of prostaglandin signaling regulates allergic airway inflammation and asthma physiology. Possible prostaglandin therapeutic targets for allergic lung inflammation and asthma will also be reviewed, as informed by human studies, basic science, and animal models.

Keywords: Allergy; Asthma; Cyclooxygenase; Lung; Prostaglandin.

Figure 1.

Synthesis of prostaglandins. Arachidonic acid is metabolized by the cyclooxygenase enzymes sequentially to PGG₂ and then PGH₂. The individual prostaglandin synthases convert PGH2 into the five primary prostanoids, PGD₂, PGE₂, PGF_2α, PGI₂, and TXA₂. Each of these prostanoids signal through distinct G protein coupled receptors (GPCR).

Figure 2.

PGD₂ signals through two GCPR, termed DP₁ and DP₂. PGD₂ signaling through DP₁ increases cAMP, while signaling through DP2 decreases cAMP.

Figure 3.

PGE₂ signals through four GCPR, termed EP₁, EP₂, EP₃, and EP₄. Signaling through EP₁ increases intracellular Ca²⁺, signaling through EP₂ increases cAMP, signaling through EP₃ decreases cAMP, and signaling through EP₄ increases cAMP.

Figure 4.

PGF_2α signals through FP to increase intracellular Ca²⁺. PGI₂ signaling through IP increases cAMP. TXA₂ signaling through TP_α increases cAMP, while signaling through TP_β decreases cAMP.