title: TNFαAffects Ciliary Beat Response to Increased Viscosity in Human Pediatric Airway Epithelium.
abstract: In airway epithelium, mucociliary clearance (MCC) velocity depends on the ciliary beat frequency (CBF), and it is affected by mucus viscoelastic properties. Local inflammation induces secretion of cytokines (TNFα) that can alter mucus viscosity; however airway ciliated cells have an autoregulatory mechanism to prevent the collapse of CBF in response to increase in mucus viscosity, mechanism that is associated with an increment in intracellular Ca+2level ([Ca2+]i). We studied the effect of TNFαon the autoregulatory mechanism that regulates CBF in response to increased viscosity using dextran solutions, in ciliated cells cultured from human pediatric epithelial adenoid tissue. Cultures were treated with TNFα, before and after the viscous load was changed. TNFαtreatment produced a significantly larger decrease in CBF in cultures exposed to dextran. Furthermore, an increment in [Ca2+]iwas observed, which was significantly larger after TNFαtreatment. In conclusion, although TNFαhas deleterious effects on ciliated cells in response to maintaining CBF after increasing viscous loading, it has a positive effect, since increasing [Ca2+]imay prevent the MCC collapse. These findings suggest that augmented levels of TNFαassociated with an inflammatory response of the nasopharyngeal epithelium may have dual effects that contribute to maintaining the effectiveness of MCC in the upper airways.
authors.affiliation: Department of Otorhinolaryngology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Claudia
authors.identifier: 0000-0003-3998-0782
authors.initials: C
authors.lastname: González
authors.affiliation: Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Karla
authors.initials: K
authors.lastname: Droguett
authors.affiliation: Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Mariana
authors.initials: M
authors.lastname: Rios
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA, USA; Surgical Services, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA.
authors.forename: Noam A
authors.initials: NA
authors.lastname: Cohen
authors.affiliation: Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Manuel
authors.identifier: 0000-0002-4307-7257
authors.initials: M
authors.lastname: Villalón
mesh_terms: D000234:Adenoids / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D002923:Cilia / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D020545:Respiratory Mucosa / Q000378:metabolism*; D046509:Tissue Culture Techniques; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*; D014783:Viscosity
chemical_list: D014409:Tumor Necrosis Factor-alpha