Altered Inhibitory Function of the E-Type Prostanoid Receptor 4 in Eosinophils and Monocytes from Aspirin-Intolerant Patients

Luschnig, Petra; Frei, Robert; Lang‐Loidolt, Doris; Rozsasi, Ajnacska; Tomazic, Peter Valentin; Lippe, Irmgard Th.; Schuligoi, Rufina; Heinemann, Ákos

doi:10.1159/000369827

Cited by 3 publications

(2 citation statements)

References 39 publications

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“…These effects were reversed by PGE 2 . We observed that the expression of the EP4 receptor in blood eosinophils tended to be reduced in AERD patients, and inhibition of eosinophil chemotaxis by PGE 2 or an EP4 agonist was less pronounced in AERD patients as compared to healthy controls (168). Single nucleotide polymorphisms of the ptger2 and ptger4 were detected in aspirin-intolerant Korean patients, predicting lower EP2 and EP4 receptor expression levels (169, 170).…”

Section: The Prostanoid—eosinophil Axis In Non-allergic Diseasesmentioning

confidence: 85%

Prostaglandins and Their Receptors in Eosinophil Function and As Therapeutic Targets

2017

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Of the known prostanoid receptors, human eosinophils express the prostaglandin D2 (PGD2) receptors DP1 [also D-type prostanoid (DP)] and DP2 (also chemoattractant receptor homologous molecule, expressed on Th2 cells), the prostaglandin E2 receptors EP2 and EP4, and the prostacyclin (PGI2) receptor IP. Prostanoids can bind to either one or multiple receptors, characteristically have a short half-life in vivo, and are quickly degraded into metabolites with altered affinity and specificity for a given receptor subtype. Prostanoid receptors signal mainly through G proteins and naturally activate signal transduction pathways according to the G protein subtype that they preferentially interact with. This can lead to the activation of sometimes opposing signaling pathways. In addition, prostanoid signaling is often cell-type specific and also the combination of expressed receptors can influence the outcome of the prostanoid impulse. Accordingly, it is assumed that eosinophils and their (patho-)physiological functions are governed by a sensitive prostanoid signaling network. In this review, we specifically focus on the functions of PGD2, PGE2, and PGI2 and their receptors on eosinophils. We discuss their significance in allergic and non-allergic diseases and summarize potential targets for drug intervention.

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Section: The Prostanoid—eosinophil Axis In Non-allergic Diseasesmentioning

confidence: 85%

Prostaglandins and Their Receptors in Eosinophil Function and As Therapeutic Targets

2017

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“…(Ying et al, 2006) While there was no difference in EP 4 expression on eosinophils between AERD subjects and healthy control, inhibition of eosinophil chemotaxis by PGE 2 or an EP 4 receptor agonist (CAY 10598) was reduced in eosinophils from AERD subjects compared to healthy controls. (Luschnig et al, 2014) The oral PGE 1 analogue, misoprostol, did not protect against NSAID-induced AERD symptoms;(Walters, Simon, Woessner, Wineinger, & White, 2017) however, newer PGE 2 agonists should be examined to evaluate this pathway for treatment of AERD.…”

Section: Individual Pgsmentioning

confidence: 99%

Prostaglandins in asthma and allergic diseases

Peebles

2019

Pharmacology & Therapeutics

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Prostaglandins are synthesized through the metabolism of arachidonic acid via the cyclooxygenase pathway. There are five primary prostaglandins, PGD, PGE, PGF, PGI, and thromboxane B, 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.

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Cellular interactions in aspirin-exacerbated respiratory disease

Badrani

Doherty

2020

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of review The purpose of this review is to summarize the complex cellular interactions of aspirin-exacerbated respiratory disease (AERD) and how these interactions promote pathogenic mechanisms of AERD. Recent findings In addition to characteristic changes in eicosanoid levels, recent studies have identified increases in alarmin cytokines (IL-33, thymic stromal lymphopoietin) as well as activated innate lymphoid and plasma cell populations in samples from AERD patients. Summary Patients with AERD typically demonstrate high levels of proinflammatory eicosanoids including cysteinyl leukotrienes (CysLTs) and prostaglandin D2 (PGD2) and hyporesponsiveness to prostaglandin E2 (PGE2). CysLTs are released by mast cells, eosinophils, and adherent platelets and promote epithelial release of IL-33, which activates mast cells and group 2 innate lymphoid cells (ILC2s) in concert with CysLTs. TSLP induces PGD2 release from mast cells which activates and recruits eosinophils, basophils, Th2 cells, and ILC2s via CRTH2. In turn, ILC2s and other cell types produce Th2 cytokines IL-4, IL-5, and IL-13 that, along with CysLTs and PGD2, promote bronchoconstriction, eosinophilic tissue inflammation, and mucus production.

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Altered Inhibitory Function of the E-Type Prostanoid Receptor 4 in Eosinophils and Monocytes from Aspirin-Intolerant Patients

Cited by 3 publications

References 39 publications

Prostaglandins and Their Receptors in Eosinophil Function and As Therapeutic Targets

Prostaglandins and Their Receptors in Eosinophil Function and As Therapeutic Targets

Prostaglandins in asthma and allergic diseases

Cellular interactions in aspirin-exacerbated respiratory disease

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