ST6GAL1 and α2-6 Sialylation Regulates IL-6 Expression and Secretion in Chronic Obstructive Pulmonary Disease

Frontiers in Immunology

James M. Wells¹  Molly Easter²  Rennan Zaharias²  Rebecca Denson²  Seth Bollenbecker²  E. Scott Helton²  Shia Vang²  Phillip Cochran²  Elex Harris³  Jarrod W. Barnes³  Stefanie Krick³ 

[1] Birmingham VA Medical Center, Birmingham, AL, United States;Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL, United States;Gregory Fleming James Cystic Fibrosis Research Center, The University of Alabama at Birmingham, Birmingham, AL, United States;UAB Lung Health Center, Birmingham, AL, United States;

关键词: ST6GAL1;    COPD;    cigarette smoke;    bronchial epithelium;    inflammation;   

DOI  :  10.3389/fimmu.2021.693149

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown