{"doi":"10.3389/fimmu.2021.693149","title":"ST6GAL1 and α2-6 Sialylation Regulates IL-6 Expression and Secretion in Chronic Obstructive Pulmonary Disease","abstract":"Chronic obstructive pulmonary disease (COPD) is a systemic disease strongly associated with cigarette smoking, airway inflammation, and acute disease exacerbations. Changes in terminal sialylation and fucosylation of asparagine (N)-linked glycans have been documented in COPD, but the role that glycosyltransferases may play in the regulation of N-linked glycans in COPD has not been fully elucidated. Recent studies suggest that modulation of ST6GAL1 (ST6 beta-galactoside alpha-2,6-sialyltransferase-1), which catalyzes terminal α2-6 sialylation of cellular proteins, may regulate inflammation and contribute to COPD phenotype(s). Interestingly, it has been previously demonstrated that ST6GAL1, a Golgi resident protein, can be proteolytically processed by BACE1 (beta-site amyloid precursor protein cleaving enzyme-1) to a circulating form that retains activity. In this study, we showed that loss of ST6GAL1 expression increased interleukin (IL)-6 expression and secretion in human bronchial epithelial cells (HBECs). Furthermore, exposure to cigarette smoke medium/extract (CSE) or BACE1 inhibition resulted in decreased ST6GAL1 secretion, reduced α2-6 sialylation, and increased IL-6 production in HBECs. Analysis of plasma ST6GAL1 levels in a small COPD patient cohort demonstrated an inverse association with prospective acute exacerbations of COPD (AECOPD), while IL-6 was positively associated. Altogether, these results suggest that reduced ST6GAL1 and α2-6 sialylation augments IL-6 expression/secretion in HBECs and is associated with poor clinical outcomes in COPD.","journal":"Frontiers in Immunology","year":2021,"id":170191,"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":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"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":416607,"name":"E. Scott Helton","orcid":"0000-0002-9954-8222","position":1,"is_corresponding":false},{"id":267596,"name":"Molly Easter","orcid":"0000-0001-8208-7266","position":2,"is_corresponding":false},{"id":267597,"name":"Seth Bollenbecker","orcid":"0000-0001-5536-2744","position":3,"is_corresponding":false},{"id":417249,"name":"Rebecca Denson","orcid":null,"position":4,"is_corresponding":false},{"id":417250,"name":"Rennan Zaharias","orcid":null,"position":5,"is_corresponding":false},{"id":702298,"name":"Phillip Cochran","orcid":"0009-0003-4277-7272","position":6,"is_corresponding":false},{"id":702299,"name":"Shia Vang","orcid":"0000-0002-2971-3560","position":7,"is_corresponding":false},{"id":361819,"name":"Elex S. Harris","orcid":"0000-0002-1444-6463","position":8,"is_corresponding":false},{"id":267138,"name":"J. Michael Wells","orcid":"0000-0001-9612-5454","position":9,"is_corresponding":false},{"id":267598,"name":"Jarrod W. Barnes","orcid":"0000-0002-1027-6591","position":10,"is_corresponding":false},{"id":267599,"name":"Stefanie Krick","orcid":"0000-0002-8284-6768","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-18T23:46:19.728805Z","pmid":"34290711","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":[]}