title: Tumor necrosis factor alpha induces a serotonin dependent early increase in ciliary beat frequency and epithelial transport velocity in murine tracheae.
abstract: The tracheal epithelium prevents via its highly effective clearance mechanism the contamination of the lower airways by pathogens. This mechanism is driven by ciliary bearing cells which are not only in contact with the gas phase; in addition they are also influenced by inflammatory mediators. These mediators can alter the protective function of the epithelium. Since the pro-inflammatoric cytokine tumor necrosis factor-α (TNF-α) plays a pivotal role within the inflammatory cascade, we investigated its effect onto the tracheal epithelium measured by its ciliary beat frequency and the particle transport velocity. In organ explant experiments the ciliary beat frequency and the particle transport velocity were measured under the application of TNF-α using tracheae from male C57BL6J mice. We observed a dose dependent TNF-α induced increase of both particle transport velocity and ciliary beat frequency. Knock out mice experiments made evident that the increase was depended on the expression of tumor necrosis factor receptor 1 (TNF-R1). The increases in ciliary beat frequency as well as the accelerated particle transport velocity were either inhibited by the unspecific serotonin antagonist methysergide or by cyproheptadine a specific 5-HT2 receptor antagonist. Thus, acetylcholine antagonists or nitric oxide synthase (NOS) inhibitors failed to inhibit the TNF-α induced activation. In conclusion, TNF-α may play a pivotal role in the protection of lower airways by inducing ciliary activity and increase in particle transport velocity via TNF-R1 and 5-HT2 receptor.
authors.affiliation: Department of Anaesthesiology, Intensive Care Medicine, Pain Therapy, Justus-Liebig-University Giessen, Giessen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Weiterer
authors.affiliation: Department of Anaesthesiology, Intensive Care Medicine, Pain Therapy, Justus-Liebig-University Giessen, Giessen, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Schulte
authors.affiliation: Department of Anaesthesiology, Intensive Care Medicine, Pain Therapy, Justus-Liebig-University Giessen, Giessen, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Müller
authors.affiliation: Department of Anaesthesiology, Intensive Care Medicine, Pain Therapy, Justus-Liebig-University Giessen, Giessen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kohlen
authors.affiliation: Department of Anaesthesiology, Intensive Care Medicine, Pain Therapy, Justus-Liebig-University Giessen, Giessen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Uhle
authors.affiliation: Department of Anaesthesiology, Intensive Care Medicine, Pain Therapy, Justus-Liebig-University Giessen, Giessen, Germany.
authors.forename: Markus A
authors.initials: MA
authors.lastname: Weigand
authors.affiliation: Department of Anaesthesiology, Intensive Care Medicine, Pain Therapy, Justus-Liebig-University Giessen, Giessen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Henrich
mesh_terms: D000818:Animals; D002924:Ciliary Body / Q000378:metabolism / Q000503:physiopathology; D004848:Epithelium / Q000378:metabolism / Q000503:physiopathology; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D009924:Organ Culture Techniques; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D014132:Trachea / Q000378:metabolism / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D044348:Receptors, Serotonin, 5-HT2; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D012701:Serotonin