Neuropeptide regulation of secretion and inflammation in human airway gland serous cells
Airway submucosal gland serous cells are sites of expression of the cystic fibrosis transmembrane conductance regulator (CFTR) and are important for fluid secretion in conducting airways. To elucidate how neuropeptides regulate serous cells, we tested if human nasal turbinate serous cells secrete bi...
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Published in | The European respiratory journal Vol. 55; no. 4; p. 1901386 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
01.04.2020
|
Online Access | Get full text |
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Summary: | Airway submucosal gland serous cells are sites of expression of the cystic fibrosis transmembrane conductance regulator (CFTR) and are important for fluid secretion in conducting airways. To elucidate how neuropeptides regulate serous cells, we tested if human nasal turbinate serous cells secrete bicarbonate (HCO
), important for mucus polymerisation and antimicrobial peptide function, during stimulation with cAMP-elevating vasoactive intestinal peptide (VIP) and if this requires CFTR. Serous cells stimulated with VIP exhibited a ∼15-20% cAMP-dependent decrease in cell volume and a ∼0.15 unit decrease in intracellular pH (pH
), reflecting activation of Cl
and HCO
secretion, respectively. HCO
secretion was directly dependent on CFTR and was absent in cells from CF patients. In contrast, neuropeptide Y (NPY) reduced VIP-evoked cAMP increases, CFTR activation, and Cl
/HCO
secretion. Culture of primary serous cells in a model that maintained a serous phenotype confirmed the activating and inhibiting effects of VIP and NPY, respectively, on fluid and HCO
secretion. Moreover, VIP enhanced antimicrobial peptide secretion and antimicrobial efficacy of secretions while NPY reduced antimicrobial efficacy. In contrast, NPY enhanced cytokine release while VIP reduced cytokine release through a mechanism requiring CFTR. As levels of VIP and NPY are up-regulated in diseases like allergy, asthma, and chronic rhinosinusitis, the balance of these two peptides in the airway may control mucus rheology and inflammatory responses in serous cells. Furthermore, the loss of CFTR conductance in serous cells may contribute to CF pathophysiology by increasing serous cells inflammatory responses in addition to directly impairing Cl
and HCO
secretion. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author Contributions: D.B.M., R.M.C., M.A.K., and R.J.L. performed experiments and analyzed data. R.M.C., M.A.K., C.C.L.T., P.P., N.D.A., and J.N.P. aided with tissue procurement, primary cell acquisition and culture, maintenance of clinical records, and intellectually contributed. D.B.M., R.M.C., and R.J.L. drafted the manuscript with critical input and approval from all authors. |
ISSN: | 0903-1936 1399-3003 |
DOI: | 10.1183/13993003.01386-2019 |