{"doi":"10.3390/ijms251810107","title":"RAMP1 Signaling Mitigates Acute Lung Injury by Distinctively Regulating Alveolar and Monocyte-Derived Macrophages","abstract":"<jats:p>Acute respiratory distress syndrome (ARDS) is a life-threatening lung injury that induces cytokine hypersecretion. Receptor activity-modifying protein (RAMP) 1, a subunit of the calcitonin gene-related peptide (CGRP) receptor, regulates the production of cytokines. This study examined the role of RAMP1 signaling during lipopolysaccharide (LPS)-induced acute lung injury (ALI). LPS administration to wild-type (WT) mice depleted alveolar macrophages (AMs) and recruited monocyte-derived macrophages (MDMs) and neutrophils. RAMP1-deficient (RAMP1−/−) mice exhibited higher lung injury scores, cytokine levels, and cytokine-producing neutrophil infiltration. RAMP1-deficient AMs produced more cytokines in response to LPS than WT AMs. Adoptive transfer of RAMP1-deficient AMs to RAMP1−/− mice increased cytokine levels and neutrophil accumulation compared to the transfer of WT AMs. RAMP1−/− mice had reduced MDM recruitment and lower pro-inflammatory and reparative macrophage profiles. Cultured bone marrow (BM)-derived RAMP1-deficient macrophages stimulated with LPS showed decreased expression of pro-inflammatory and pro-repairing genes. CGRP administration to WT mice reduced cytokine production and neutrophil accumulation. These findings indicate that RAMP1 signaling mitigates LPS-induced ALI by inactivating AMs and promoting inflammatory and repair activities of MDMs. Targeting RAMP1 signaling presents a potential therapeutic approach for the treatment of ARDS.</jats:p>","journal":"International Journal of Molecular Sciences","year":2024,"id":636841,"datarank":0.37273599746820013,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.0,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":675866,"name":"Yoshiya Ito","orcid":"0000-0001-5258-2098","position":1,"is_corresponding":false},{"id":1653250,"name":"Mayuko Osada","orcid":null,"position":2,"is_corresponding":false},{"id":1653251,"name":"Hiromi Matsuda","orcid":null,"position":3,"is_corresponding":false},{"id":676377,"name":"Kanako Hosono","orcid":null,"position":4,"is_corresponding":false},{"id":86986,"name":"Kazutake Tsujikawa","orcid":"0000-0003-1870-9790","position":5,"is_corresponding":false},{"id":1653252,"name":"Hirotsugu Okamoto","orcid":null,"position":6,"is_corresponding":false},{"id":675872,"name":"Hideki Amano","orcid":"0000-0003-0855-1889","position":7,"is_corresponding":false},{"id":940300,"name":"Atsushi Yamashita","orcid":"0009-0008-6576-3558","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"RAMP1 Signaling Mitigates Acute Lung Injury by Distinctively Regulating Alveolar and Monocyte-Derived Macrophages","abstract":"<jats:p>Acute respiratory distress syndrome (ARDS) is a life-threatening lung injury that induces cytokine hypersecretion. Receptor activity-modifying protein (RAMP) 1, a subunit of the calcitonin gene-related peptide (CGRP) receptor, regulates the production of cytokines. This study examined the role of RAMP1 signaling during lipopolysaccharide (LPS)-induced acute lung injury (ALI). LPS administration to wild-type (WT) mice depleted alveolar macrophages (AMs) and recruited monocyte-derived macrophages (MDMs) and neutrophils. RAMP1-deficient (RAMP1−/−) mice exhibited higher lung injury scores, cytokine levels, and cytokine-producing neutrophil infiltration. RAMP1-deficient AMs produced more cytokines in response to LPS than WT AMs. Adoptive transfer of RAMP1-deficient AMs to RAMP1−/− mice increased cytokine levels and neutrophil accumulation compared to the transfer of WT AMs. RAMP1−/− mice had reduced MDM recruitment and lower pro-inflammatory and reparative macrophage profiles. Cultured bone marrow (BM)-derived RAMP1-deficient macrophages stimulated with LPS showed decreased expression of pro-inflammatory and pro-repairing genes. CGRP administration to WT mice reduced cytokine production and neutrophil accumulation. These findings indicate that RAMP1 signaling mitigates LPS-induced ALI by inactivating AMs and promoting inflammatory and repair activities of MDMs. Targeting RAMP1 signaling presents a potential therapeutic approach for the treatment of ARDS.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39337592","pmcid":"PMC11432488","openalex_id":null,"authors":[],"funders":[{"funder_name":"Japanese Ministry of Education, Culture, Sports, Science, and Technology (MEXT)","grant_id":"22K06651","title":null},{"funder_name":"Parents’ Association Grant of the Kitasato University School of Medicine","grant_id":"","title":null},{"funder_name":"Integrative Research Program of the Graduate School of Medical Science at Kitasato University","grant_id":"","title":null}],"total_grants":3,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/1422-0067/25/18/10107/pdf?version=1726818888","host_type":"publisher"},{"url":"https://www.mdpi.com/1422-0067/25/18/10107/pdf","host_type":"publisher"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11432488/pdf/ijms-25-10107.pdf","host_type":"repository"},{"url":"https://doi.org/10.3390/ijms251810107","host_type":"Unpaywall"},{"url":"https://europepmc.org/articles/PMC11432488","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11432488?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Animals","Acute Lung Injury","Mice","Receptor Activity-Modifying Protein 1","Signal Transduction","Lipopolysaccharides","Macrophages, Alveolar","Cytokines","Mice, Inbred C57BL","Mice, Knockout","Male","Macrophages","Neutrophils"],"mesh_terms":["Neutrophils","Macrophages","Macrophages, Alveolar","Animals","Mice, Inbred C57BL","Mice, Knockout","Mice","Lipopolysaccharides","Cytokines","Signal Transduction","Male","Acute Lung Injury","Receptor Activity-Modifying Protein 1"],"keywords":["Macrophage","Nerve","Immunity","neutrophil","Ramp1"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T17:50:30.551513Z","pmid":null,"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":[]}