title: Relaxin stimulates bronchial epithelial cell PKA activation, migration, and ciliary beating.
abstract: Relaxin is an insulin-like serum protein secreted during pregnancy and found in many tissues, including the lung. Relaxin is reported to stimulate epithelial cell proliferation, but the effects of relaxin on airway epithelium are unknown. We tested the hypothesis that relaxin would stimulate the increased migration of bronchial epithelial cells (BEC) in response to wounding. Using monolayers of BEC in a wound-healing model, relaxin augmented wound closure with maximal closure occurring at 12 hr (1 micro M). Unlike cytokines, relaxin did not stimulate increased BEC interleukin-8 (IL-8) release. Relaxin caused a significant stimulation of ciliary beat frequency (CBF) in BEC. Because protein kinase (PKA) activation increases CBF and relaxin can elevate intracellular cAMP levels, we measured PKA activity in BEC treated with relaxin. Relaxin increased PKA activity 3-4 fold by approximately 4 hr, with a return to baseline levels by 8-10 hr. Relaxin-stimulated PKA activity differs temporally from the rapid (1 hr) beta-adrenergic activation of PKA in BEC. These data suggest that relaxin augments epithelial repair by increasing airway cell migration and CBF via PKA-dependent mechanisms.
authors.affiliation: Research Service, Department of Veterans Affairs Medical Center, Omaha, NE 68105, USA. twyatt@unmc.edu
authors.forename: T A
authors.initials: TA
authors.lastname: Wyatt
authors.forename: J H
authors.initials: JH
authors.lastname: Sisson
authors.forename: M A
authors.initials: MA
authors.lastname: Forgèt
authors.forename: R G
authors.initials: RG
authors.lastname: Bennett
authors.forename: F G
authors.initials: FG
authors.lastname: Hamel
authors.forename: J R
authors.initials: JR
authors.lastname: Spurzem
mesh_terms: D000818:Animals; D001980:Bronchi / Q000166:cytology*; D002417:Cattle; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000166:cytology; D012065:Relaxin / Q000502:physiology*
chemical_list: D012065:Relaxin; D017868:Cyclic AMP-Dependent Protein Kinases