{"doi":"10.1172/jci.insight.130771","title":"CC16 augmentation reduces exaggerated COPD-like disease in Cc16-deficient mice","abstract":"Low Club Cell 16 kDa protein (CC16) plasma levels are linked to accelerated lung function decline in patients with chronic obstructive pulmonary disease (COPD). Cigarette smoke-exposed (CS-exposed) Cc16-/- mice have exaggerated COPD-like disease associated with increased NF-κB activation in their lungs. It is unclear whether CC16 augmentation can reverse exaggerated COPD in CS-exposed Cc16-/- mice and whether increased NF-κB activation contributes to the exaggerated COPD in CS-exposed Cc16-/- lungs. CS-exposed WT and Cc16-/- mice were treated with recombinant human CC16 (rhCC16) or an NF-κB inhibitor versus vehicle beginning at the midpoint of the exposures. COPD-like disease and NF-κB activation were measured in the lungs. RhCC16 limited the progression of emphysema, small airway fibrosis, and chronic bronchitis-like disease in WT and Cc16-/- mice partly by reducing pulmonary inflammation (reducing myeloid leukocytes and/or increasing regulatory T and/or B cells) and alveolar septal cell apoptosis, reducing NF-κB activation in CS-exposed Cc16-/- lungs, and rescuing the reduced Foxj1 expression in CS-exposed Cc16-/- lungs. IMD0354 treatment reduced exaggerated lung inflammation and rescued the reduced Foxj1 expression in CS-exposed Cc16-/- mice. RhCC16 treatment reduced NF-κB activation in luciferase reporter A549 cells. Thus, rhCC16 treatment limits COPD progression in CS-exposed Cc16-/- mice partly by inhibiting NF-κB activation and represents a potentially novel therapeutic approach for COPD.","journal":"JCI Insight","year":2023,"id":330028,"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":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9514,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1053235,"name":"María Laucho-Contreras","orcid":"0000-0002-7611-0498","position":1,"is_corresponding":false},{"id":285078,"name":"Xiaoyun Wang","orcid":"0000-0002-9900-740X","position":2,"is_corresponding":false},{"id":364813,"name":"Quynh‐Anh Fucci","orcid":"0000-0002-3126-0716","position":3,"is_corresponding":false},{"id":14742,"name":"Patrick R. Burkett","orcid":"0000-0003-4472-7124","position":4,"is_corresponding":false},{"id":86984,"name":"Se-Jin Kim","orcid":"0000-0002-6704-4644","position":5,"is_corresponding":false},{"id":285079,"name":"Duo Zhang","orcid":"0000-0003-0361-4174","position":6,"is_corresponding":false},{"id":305925,"name":"Yohannes Tesfaigzi","orcid":"0000-0002-3997-5839","position":7,"is_corresponding":false},{"id":735367,"name":"Yuhong Li","orcid":"0000-0003-1684-207X","position":8,"is_corresponding":false},{"id":1053236,"name":"Abhiram R. Bhashyam","orcid":"0000-0002-9170-4745","position":9,"is_corresponding":false},{"id":291057,"name":"Li Zhang","orcid":"0000-0002-9386-8938","position":10,"is_corresponding":false},{"id":1053643,"name":"Haider Khamas","orcid":null,"position":11,"is_corresponding":false},{"id":267142,"name":"Bartolomé R. Celli","orcid":"0000-0002-7266-8371","position":12,"is_corresponding":false},{"id":691594,"name":"Aprile L. Pilon","orcid":null,"position":13,"is_corresponding":false},{"id":232045,"name":"Francesca Polverino","orcid":"0000-0001-9686-5698","position":14,"is_corresponding":false},{"id":621764,"name":"Caroline A. Owen","orcid":"0000-0003-4377-3591","position":15,"is_corresponding":false},{"id":434150,"name":"Joselyn Rojas","orcid":"0000-0003-4994-075X","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T01:09:05.843139Z","pmid":"36787195","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":[]}