PMID- 32400135
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2092-7355 (Print)
IS  - 2092-7363 (Electronic)
IS  - 2092-7355 (Linking)
VI  - 12
IP  - 4
DP  - 2020 Jul
TI  - In Vitro and In Vivo Validation of EP2-Receptor Agonism to Selectively Achieve 
      Inhibition of Mast Cell Activity.
PG  - 712-728
LID - 10.4168/aair.2020.12.4.712 [doi]
AB  - PURPOSE: Agonism of the prostaglandin E2 receptor, E-prostanoid receptor 2 (EP2), 
      may represent an alternative protective mechanism in mast cell (MC)-mediated 
      diseases. Previous studies have suggested that activation of the MC EP2 receptor 
      prevents pathological changes in the murine models of allergic asthma. This work 
      aimed to analytically validate the EP2 receptor on MCs as a therapeutic target. 
      METHODS: Murine MC lines and primary cultures, and MCs bearing the human 
      immunoglobulin E (IgE) receptor were subjected to IgE-mediated activation 
      subsequent to incubation with selective EP2 agonists. Two molecularly unrelated 
      agonists, butaprost and CP-533536, were tested either in vitro or in 2 in vivo 
      models of allergy. RESULTS: The diverse range of MC populations was consistently 
      inhibited through selective EP2 agonism in spite of exhibiting a heterogeneous 
      phenotype. Such inhibition occurred in both mouse and human IgE (hIgE)-mediated 
      activation. The use of molecularly unrelated selective EP2 agonists allowed for 
      the confirmation of the specificity of this protective mechanism. This effect was 
      further demonstrated in 2 in vivo murine models of allergy where MCs are a key to 
      pathological changes: cutaneous anaphylaxis in a transgenic mouse model 
      expressing the hIgE receptor and aeroallergen-induced murine model of asthma. 
      CONCLUSIONS: Selective EP2 agonism is a powerful pharmacological strategy to 
      prevent MCs from being activated through IgE-mediated mechanisms and from causing 
      deleterious effects. The MC EP2 receptor may be an effective pharmacological 
      target in allergic and other MC-mediated conditions.
CI  - Copyright (c) 2020 The Korean Academy of Asthma, Allergy and Clinical Immunology . 
      The Korean Academy of Pediatric Allergy and Respiratory Disease.
FAU - Plaza, Judith
AU  - Plaza J
AUID- ORCID: 0000-0003-2217-3095
AD  - Department of Pharmacology, Therapeutics and Toxicology, Universitat Autonoma de 
      Barcelona, Barcelona, Spain.
FAU - Torres, Rosa
AU  - Torres R
AUID- ORCID: 0000-0002-9109-4035
AD  - Department of Pharmacology, Therapeutics and Toxicology, Universitat Autonoma de 
      Barcelona, Barcelona, Spain.
FAU - Urbano, Adrian
AU  - Urbano A
AUID- ORCID: 0000-0002-4107-1644
AD  - Department of Pharmacology, Therapeutics and Toxicology, Universitat Autonoma de 
      Barcelona, Barcelona, Spain.
FAU - Picado, Cesar
AU  - Picado C
AUID- ORCID: 0000-0001-7400-4993
AD  - Department of Pneumology and Respiratory Allergy, Hospital Clinic i Universitari 
      de Barcelona, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), 
      CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain.
FAU - de Mora, Fernando
AU  - de Mora F
AUID- ORCID: 0000-0002-3002-6004
AD  - Department of Pharmacology, Therapeutics and Toxicology, Universitat Autonoma de 
      Barcelona, Barcelona, Spain. fernando.demora@uab.cat.
LA  - eng
PT  - Journal Article
PL  - Korea (South)
TA  - Allergy Asthma Immunol Res
JT  - Allergy, asthma & immunology research
JID - 101518382
PMC - PMC7225001
OTO - NOTNLM
OT  - IgE
OT  - allergy
OT  - anaphylaxis
OT  - asthma
OT  - inflammation
OT  - mast cell
OT  - prostaglandin E receptor 2
OT  - prostaglandin E2
COIS- There are no financial or other issues that might lead to conflict of interest.
EDAT- 2020/05/14 06:00
MHDA- 2020/05/14 06:01
PMCR- 2020/07/01
CRDT- 2020/05/14 06:00
PHST- 2019/12/12 00:00 [received]
PHST- 2020/02/27 00:00 [revised]
PHST- 2020/03/01 00:00 [accepted]
PHST- 2020/05/14 06:00 [entrez]
PHST- 2020/05/14 06:00 [pubmed]
PHST- 2020/05/14 06:01 [medline]
PHST- 2020/07/01 00:00 [pmc-release]
AID - 12.712 [pii]
AID - 10.4168/aair.2020.12.4.712 [doi]
PST - ppublish
SO  - Allergy Asthma Immunol Res. 2020 Jul;12(4):712-728. doi: 
      10.4168/aair.2020.12.4.712.