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Review
. 2018 Sep 29;19(1):189.
doi: 10.1186/s12931-018-0893-x.

The prostaglandin D2 receptor 2 pathway in asthma: a key player in airway inflammation

Christian Domingo  1   2 , Oscar Palomares  3 , David A Sandham  4 , Veit J Erpenbeck  5 , Pablo Altman  6
Affiliations
Review

The prostaglandin D2 receptor 2 pathway in asthma: a key player in airway inflammation

Christian Domingo et al. Respir Res. .

Abstract

Asthma is characterised by chronic airway inflammation, airway obstruction and hyper-responsiveness. The inflammatory cascade in asthma comprises a complex interplay of genetic factors, the airway epithelium, and dysregulation of the immune response.Prostaglandin D2 (PGD2) is a lipid mediator, predominantly released from mast cells, but also by other immune cells such as TH2 cells and dendritic cells, which plays a significant role in the pathophysiology of asthma. PGD2 mainly exerts its biological functions via two G-protein-coupled receptors, the PGD2 receptor 1 (DP1) and 2 (DP2). The DP2 receptor is mainly expressed by the key cells involved in type 2 immune responses, including TH2 cells, type 2 innate lymphoid cells and eosinophils. The DP2 receptor pathway is a novel and important therapeutic target for asthma, because increased PGD2 production induces significant inflammatory cell chemotaxis and degranulation via its interaction with the DP2 receptor. This interaction has serious consequences in the pulmonary milieu, including the release of pro-inflammatory cytokines and harmful cationic proteases, leading to tissue remodelling, mucus production, structural damage, and compromised lung function. This review will discuss the importance of the DP2 receptor pathway and the current understanding of its role in asthma.

Keywords: Airway inflammation; Asthma; Prostaglandin D2; Prostaglandin D2 receptor 2.

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Conflict of interest statement

Ethics approval and consent to participate

Not applicable

Consent for publication

Not applicable

Competing interests

Dr. Domingo reports personal fees from Novartis, GSK, AstraZeneca, and Teva, as well as non-financial support from Teva, outside of the submitted work.

Dr. Palomares reports personal fees for giving scientific lectures from Allergy Therapeutics, Amgen, AstraZenenca, Inmunotek S.L, Novartis, and Stallergenes. Dr. Palomares received grants from Inmunotek S.L under collaborative public projects and has participated in advisory boards for Novartis and Sanofi Genzyme. Everything reported is outside the submitted work.

Veit J. Erpenbeck is an employee of Novartis Pharma.

David Sandham is a full-time employee and shareholder of Novartis Institutes for Biomedical Research and Novartis, respectively.

Pablo Altman is a full-time employee of Novartis Pharmaceuticals Corporation.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Overview of the DP2 receptor-mediated response of immune cells in the inflammatory pathway. Proposed schematic providing an overview of the DP2 receptor-mediated response of various immune cells, including mast cells, TH2 cells, ILC2 and eosinophils, and the subsequent effect on inflammation in the asthmatic airways through increased inflammatory cell chemotaxis and cytokine production. Abbreviations, APC: antigen presenting cell; DP2: prostaglandin D2 receptor 2; IgE: immunoglobulin E; IL: interleukin; ILC2: type 2 innate lymphoid cell; PGD2: prostaglandin D2
See this image and copyright information in PMC

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