The role of prostaglandins in allergic lung inflammation and asthma

Abstract

Prostaglandins are products of the cyclooxygenase pathway of arachidonic acid metabolism. There are five primary prostaglandins, PGD2, PGE2, PGF2, PGI2, and thromboxane B2, all of which signal through distinct seven transmembrane, G-protein coupled receptors. Some prostaglandins may counteract the actions of others, or even the same prostaglandin may have opposing physiologic or immunologic effects, depending on the specific receptor through which it signals. In this review, we will examine the effects of cyclooxygenase activity and the various prostaglandins on allergic airway inflammation and physiology that is associated with asthma. We also highlight the potential therapeutic benefit of targeting prostaglandins in allergic lung inflammation and asthma based on basic science, animal model, and human studies.

Lipid Mediator Regulation of Group 2 Innate Lymphoid Cells

“…PGI 2 has a well-established correlation to allergic disorders, as several studies in mice have shown that PGI 2 administration diminishes features of allergic and asthmatic airways including airway eosinophilia, Th2 cytokine production, and AHR, while PGI 2 signaling deficiency leads to exaggerated allergic inflammation [51][52][53][54]. In addition, it has been shown that PGI 2 levels are elevated in the lungs of individuals during allergic inflammation, which demonstrates that PGI 2 is present during allergic inflammation in humans [26]. Therefore, PGI 2 is considered an important player in the regulation and dampening of Th2 inflammation.…”

“…Eicosanoids have long since been associated with Th2 inflammatory diseases and share a common origin, from arachidonic acid [25][26][27]. Arachidonic acid can be metabolized into downstream prostaglandins by the cyclooxygenase enzymes, COX-1 and COX-2, and to leukotrienes by the 5-lipoxygenase enzyme.…”

“…PGD 2 is strongly correlated to a variety of allergic disorders, as it is generated by eosinophils and in large quantities by IgE-activated mast cells [26]. Therefore, it is not surprising that studies have shown the PGD 2 signaling pathway plays a role in allergic rhinitis, asthma [31,32] atopic dermatitis [33,34] CRS and nasal polyposis [35][36][37], and aspirin exacerbated respiratory disease (AERD) [38].…”

“…Similarly to other prostaglandins, PGI 2 is generated from arachidonic acid metabolism through the cyclooxygenase enzymes, however it also requires downstream conversion by PGI synthase (PGIS) [26]. PGI 2 is also known as prostacylin, and signals through the prostacylin receptor, IP.…”

Therapeutic immunomodulation with mesenchymal stromal cells: the need for in vivo clues

“…Prostaglandins have a variety of physiological and immunological effects [53,54]. PGE2 in particular supports phagocyte-mediated inflammation but can also skew type 1 into type 2 immune responses or enhance immunosuppressive activity of Treg and MDSC [55].…”