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Primary normal human bronchial epithelial cells (HBEs) grown at air-liquid interface and wild-type (wt)CFBE41o- cells (expressing wtCFTR) were exposed to cell-free NETs from unrelated healthy volunteers for 18 h in vitro. Cytokines were measured in the apical supernatant by Luminex, and the effect on the HBE transcriptome was assessed by RNA sequencing. NETs consistently stimulated IL-8, TNF-\u03b1, and IL-1\u03b1 secretion by HBEs from multiple donors, with variable effects on other cytokines (IL-6, G-CSF, and GM-CSF). Expression of HBE RNAs encoding IL-1 family cytokines, particularly IL-36 subfamily members, was increased in response to NETs. NET exposure in the presence of anakinra [recombinant human IL-1 receptor antagonist (rhIL-1RA)] dampened NET-induced changes in IL-8 and TNF-\u03b1 proteins as well as IL-36\u03b1 RNA. rhIL-36RA limited the increase in expression of proinflammatory cytokine RNAs in HBEs exposed to NETs. NETs selectively upregulate an IL-1 family cytokine response in HBEs, which enhances IL-8 production and is limited by rhIL-1RA. The present findings describe a unique mechanism by which NETs may contribute to inflammation in human lung disease in vivo. NET-driven IL-1 signaling may represent a novel target for modulating inflammation in diseases characterized by a substantial NET burden. <\/jats:p>","DOI":"10.1152\/ajplung.00144.2019","type":"journal-article","created":{"date-parts":[[2020,3,11]],"date-time":"2020-03-11T17:46:13Z","timestamp":1583948773000},"page":"L137-L147","source":"Crossref","is-referenced-by-count":63,"title":["Neutrophil extracellular traps activate IL-8 and IL-1 expression in human bronchial epithelia"],"prefix":"10.1152","volume":"319","author":[{"given":"Kristin M.","family":"Hudock","sequence":"first","affiliation":[{"name":"Division of Adult Pulmonary & Critical Care Medicine, University of Cincinnati, Cincinnati, Ohio"},{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio"},{"name":"Division of Pulmonary Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret S.","family":"Collins","sequence":"additional","affiliation":[{"name":"Division of Adult Pulmonary & Critical Care Medicine, University of Cincinnati, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Imbrogno","sequence":"additional","affiliation":[{"name":"Division of Adult Pulmonary & Critical Care Medicine, University of Cincinnati, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Snowball","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth L.","family":"Kramer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio"},{"name":"Division of Pulmonary Medicine, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Brewington","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio"},{"name":"Division of Pulmonary Medicine, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kandace","family":"Gollomp","sequence":"additional","affiliation":[{"name":"Division of Hematology, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cormac","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia J.","family":"Ostmann","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J.","family":"Kopras","sequence":"additional","affiliation":[{"name":"Division of Adult Pulmonary & Critical Care Medicine, University of Cincinnati, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia R.","family":"Davidson","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anusha","family":"Srdiharan","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paritha","family":"Arumugam","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio"},{"name":"Division of Pulmonary Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaon","family":"Sengupta","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2025-027X","authenticated-orcid":false,"given":"Yan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio"},{"name":"Division of Pulmonary Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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