Prostaglandin Regulation in Airway Inflammation

Prostaglandins are a family of lipid mediators derived from arachidonic acid that exert both pro-inflammatory and anti-inflammatory actions within the airway. Synthesis is initiated by cyclooxygenase enzymes, leading to the production of distinct prostaglandins such as PGE2, PGI2 and PGD2, each acting through discrete G-protein-coupled receptors (designated EP1–4, IP and DP respectively). In healthy airways, a balance of these mediators maintains tissue homeostasis and regulates smooth muscle tone, vascular permeability and immune cell recruitment. In chronic airway diseases such as asthma and chronic rhinosinusitis, dysregulation of prostaglandin production or receptor signalling contributes to persistent eosinophilic inflammation, airway hyperresponsiveness and remodelling. Elevated levels of pro-inflammatory prostaglandins may amplify type-2 cytokine responses and IgE production, whereas engagement of specific receptors (for example EP2 or EP4) can suppress cytokine release, reduce leucocyte infiltration and promote resolution. Understanding the cellular and molecular circuitry of prostaglandin receptor subtypes has therefore become pivotal to the design of novel therapies aimed at restoring inflammatory balance in respiratory disease.

Research from Nature Portfolio

A foundational study has delineated the role of the PGE2–EP2 axis in driving IgE class switching and allergic airway inflammation. In models of ovalbumin-induced asthma, genetic deletion of the EP2 receptor markedly reduced levels of circulating IgE, attenuated airway eosinophilia and ameliorated lung histopathology. Mechanistic analysis revealed that PGE2 engagement of EP2 enhances STAT6 phosphorylation in response to IL-4, thereby promoting transcription of germline ε transcripts and activation-induced cytidine deaminase. These findings established the PGE2-EP2-STAT6 pathway as a key amplifier of allergic sensitisation and have underpinned subsequent efforts to develop selective EP2 modulators as potential interventions for atopic asthma.

Prostaglandin Regulation in Airway Inflammation publication trend

The graph below shows the total number of articles in prostaglandin regulation in airway inflammation across all publications each year (not limited to Nature Index journals).

Technical terms

Eicosanoids: Bioactive lipids derived from arachidonic acid, including prostaglandins and leukotrienes, that mediate inflammation.

PGE2 (Prostaglandin E2): A key prostaglandin with pleiotropic effects on immune cells, smooth muscle and vascular tone via EP1–EP4 receptors.

EP Receptors: G-protein-coupled receptors (EP1–EP4) specific for PGE2, each linked to distinct intracellular signalling pathways.

Myeloid-Derived Suppressor Cells (MDSCs): A heterogeneous population of immunoregulatory cells that suppress T-cell responses and modulate inflammation.

Airway Hyperresponsiveness (AHR): An exaggerated bronchoconstrictive response to stimuli, characteristic of asthma and measured by changes in lung function.

References

1. Prostaglandins E2 signal mediated by receptor subtype EP2 promotes IgE production in vivo and contributes to asthma development. Scientific Reports (2016).
2. Systemic EP4 receptor agonist and Arginase‐1 therapy in a murine model of chronic asthma and influenza virus‐induced asthma exacerbation. British Journal of Pharmacology (2025).
3. Activation of the PGE2–EP2 pathway as a potential drug target for treating eosinophilic rhinosinusitis. Frontiers in Immunology (2024).