{"doi":"10.1016/j.jaci.2020.03.004","title":"RGS4 promotes allergen- and aspirin-associated airway hyperresponsiveness by inhibiting PGE2 biosynthesis","abstract":"Background Allergens elicit host production of mediators acting on G-protein–coupled receptors to regulate airway tone. Among these is prostaglandin E2 (PGE2), which, in addition to its role as a bronchodilator, has anti-inflammatory actions. Some patients with asthma develop bronchospasm after the ingestion of aspirin and other nonsteroidal anti-inflammatory drugs, a disorder termed aspirin-exacerbated respiratory disease. This condition may result in part from abnormal dependence on the bronchoprotective actions of PGE2. Objective We sought to understand the functions of regulator of G protein signaling 4 (RGS4), a cytoplasmic protein expressed in airway smooth muscle and bronchial epithelium that regulates the activity of G-protein–coupled receptors, in asthma. Methods We examined RGS4 expression in human lung biopsies by immunohistochemistry. We assessed airways hyperresponsiveness (AHR) and lung inflammation in germline and airway smooth muscle–specific Rgs4 −/− mice and in mice treated with an RGS4 antagonist after challenge with Aspergillus fumigatus . We examined the role of RGS4 in nonsteroidal anti-inflammatory drug–associated bronchoconstriction by challenging aspirin-exacerbated respiratory disease–like ( ptges1 −/− ) mice with aspirin. Results RGS4 expression in respiratory epithelium is increased in subjects with severe asthma. Allergen-induced AHR was unexpectedly diminished in Rgs4 −/− mice, a finding associated with increased airway PGE2 levels. RGS4 modulated allergen-induced PGE2 secretion in human bronchial epithelial cells and prostanoid-dependent bronchodilation. The RGS4 antagonist CCG203769 attenuated AHR induced by allergen or aspirin challenge of wild-type or ptges1 −/− mice, respectively, in association with increased airway PGE2 levels. Conclusions RGS4 may contribute to the development of AHR by reducing airway PGE2 biosynthesis in allergen- and aspirin-induced asthma.","journal":"Journal of Allergy and Clinical Immunology","year":2020,"id":76287,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9493,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":105273,"name":"Jamie Redes","orcid":"0000-0002-7204-6257","position":1,"is_corresponding":false},{"id":397802,"name":"Nariman Balenga","orcid":"0000-0002-2741-9595","position":2,"is_corresponding":false},{"id":370479,"name":"Morgan McCullough","orcid":null,"position":3,"is_corresponding":false},{"id":397803,"name":"Nathalie Fuentes","orcid":"0000-0002-2075-4219","position":4,"is_corresponding":false},{"id":398816,"name":"Ameya Gokhale","orcid":null,"position":5,"is_corresponding":false},{"id":360857,"name":"Cynthia Koziol‐White","orcid":"0000-0003-1101-2747","position":6,"is_corresponding":false},{"id":397804,"name":"Joseph A. Jude","orcid":"0000-0003-3083-0489","position":7,"is_corresponding":false},{"id":397805,"name":"Laura A. Madigan","orcid":"0000-0002-5786-8420","position":8,"is_corresponding":false},{"id":397806,"name":"Eunice C. Chan","orcid":"0000-0003-0599-5898","position":9,"is_corresponding":false},{"id":398817,"name":"William H. Jester","orcid":null,"position":10,"is_corresponding":false},{"id":398818,"name":"Sabrina Biardel","orcid":null,"position":11,"is_corresponding":false},{"id":397807,"name":"Nicolas Flamand","orcid":"0000-0001-5944-7200","position":12,"is_corresponding":false},{"id":247084,"name":"Reynold A. Panettieri","orcid":"0000-0003-0834-4636","position":13,"is_corresponding":false},{"id":369508,"name":"Kirk M. Druey","orcid":"0000-0002-5834-6501","position":14,"is_corresponding":false},{"id":398815,"name":"Gordon S. Wong","orcid":null,"position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-18T21:47:46.469293Z","pmid":"32199913","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}