{"doi":"10.1152/ajpcell.00112.2020","title":"TNFα and IL-17 alkalinize airway surface liquid through CFTR and pendrin","abstract":"The pH of airway surface liquid (ASL) is a key factor that determines respiratory host defense; ASL acidification impairs and alkalinization enhances key defense mechanisms. Under healthy conditions, airway epithelia secrete base ([Formula: see text]) and acid (H + ) to control ASL pH (pH ASL ). Neutrophil-predominant inflammation is a hallmark of several airway diseases, and TNFα and IL-17 are key drivers. However, how these cytokines perturb pH ASL regulation is uncertain. In primary cultures of differentiated human airway epithelia, TNFα decreased and IL-17 did not change pH ASL . However, the combination (TNFα+IL-17) markedly increased pH ASL by increasing [Formula: see text] secretion. TNFα+IL-17 increased expression and function of two apical [Formula: see text] transporters, CFTR anion channels and pendrin Cl − /[Formula: see text] exchangers. Both were required for maximal alkalinization. TNFα+IL-17 induced pendrin expression primarily in secretory cells where it was coexpressed with CFTR. Interestingly, significant pendrin expression was not detected in CFTR-rich ionocytes. These results indicate that TNFα+IL-17 stimulate [Formula: see text] secretion via CFTR and pendrin to alkalinize ASL, which may represent an important defense mechanism in inflamed airways.","journal":"American Journal of Physiology-Cell Physiology","year":2020,"id":93289,"datarank":0.5570358100056463,"base_score":3.713572066704308,"endowment":3.713572066704308,"self_citation_contribution":0.5570358100056463,"citation_network_contribution":0.0,"self_endowment_contribution":0.5570358100056463,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":40,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9495,"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":413457,"name":"Ian M. Thornell","orcid":"0000-0001-5535-2925","position":1,"is_corresponding":false},{"id":246349,"name":"Alejandro A. Pezzulo","orcid":"0000-0001-7544-5109","position":2,"is_corresponding":false},{"id":246348,"name":"Andrew L. Thurman","orcid":"0000-0002-7777-4165","position":3,"is_corresponding":false},{"id":465068,"name":"Guillermo S. Romano Ibarra","orcid":"0000-0003-4723-2055","position":4,"is_corresponding":false},{"id":401888,"name":"Philip H. Karp","orcid":"0009-0000-7642-1141","position":5,"is_corresponding":false},{"id":246351,"name":"Ping Tan","orcid":"0000-0002-7445-3577","position":6,"is_corresponding":false},{"id":466724,"name":"Michael E. Duffey","orcid":null,"position":7,"is_corresponding":false},{"id":401889,"name":"Michael J. Welsh","orcid":"0000-0002-1646-6206","position":8,"is_corresponding":false},{"id":439921,"name":"Tayyab Rehman","orcid":"0000-0001-7792-201X","position":0,"is_corresponding":true}],"reference_count":95,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T22:30:54.208860Z","pmid":"32432926","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":[]}