{"doi":"10.1101/2021.09.23.461540","title":"Tobramycin-induced secretion of <i>P. aeruginosa</i> 5′ tRNA-fMet halves suppresses lung inflammation via AGO2 gene silencing","abstract":"Abstract Although inhaled tobramycin increases lung function in people with cystic fibrosis (pwCF), the density of P. aeruginosa in the lungs is only modestly reduced by tobramycin; hence, the mechanism whereby tobramycin improves lung function is unclear. Here, we demonstrate that tobramycin increases the abundance of two 5′ tRNA-fMet halves in outer membrane vesicles (OMVs) secreted by P. aeruginosa and that the 5′ tRNA-fMet halves reduce IL-8 secretion by CF bronchial epithelial cells (CF-HBECs). In mouse lung, the 5′ tRNA-fMet halves attenuate KC secretion and neutrophil recruitment. We also report that the 5′ tRNA-fMet halves suppress pro-inflammatory network gene expression by an Argonaut 2 (AGO2)-mediated gene silencing mechanism, thereby reducing IL-8 secretion in CF-HBECs. Moreover, tobramycin reduces the IL-8 concentration and neutrophil content in bronchoalveolar lavage fluid of pwCF. Thus, we conclude that tobramycin improves lung function in part by reducing chronic inflammation and neutrophil-mediated lung damage in pwCF.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":221624,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":472045,"name":"Katja Koeppen","orcid":"0000-0003-1094-0621","position":1,"is_corresponding":false},{"id":473825,"name":"Alix Ashare","orcid":"0000-0002-2413-5845","position":2,"is_corresponding":false},{"id":456,"name":"Deborah A. Hogan","orcid":"0000-0002-6366-2971","position":3,"is_corresponding":false},{"id":393304,"name":"Scott A. Gerber","orcid":"0000-0002-2964-5051","position":4,"is_corresponding":false},{"id":65140,"name":"BRUCE A. STANTON","orcid":"0000-0002-1661-407X","position":5,"is_corresponding":false},{"id":655833,"name":"Zhongyou Li","orcid":"0000-0002-0196-2979","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:53:55.215284Z","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":[]}