title: Effect of secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related peptide-1 (SLURP-1) on airway epithelial cells.
abstract: Acetylcholine (ACh) exerts various anti-inflammatory effects through α7 nicotinic ACh receptors (nAChRs). We have previously shown that secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related peptide-1 (SLURP-1), a positive allosteric modulator of α7 nAChR signaling, is down-regulated both in an animal model of asthma and in human epithelial cells treated with an inflammatory cytokine related to asthma. Our aim of this study was to explore the effect of SLURP-1, signal through α7 nAChR, in the pathophysiology of airway inflammation. Cytokine production was examined using human epithelial cells. Ciliary beat frequency of murine trachea was measured using a high speed camera. The IL-6 and TNF-α production by human epithelial cells was augmented by siRNA of SLURP-1 and α7 nicotinic ACh receptor. The cytokine production was also dose-dependently suppressed by human recombinant SLURP-1 (rSLURP-1). The ciliary beat frequency and amplitude of murine epithelial cells were augmented by PNU282987, a selective α7 nAChR agonist. Those findings suggested that SLURP-1 and stimulus through α7 nicotinic ACh receptors actively controlled asthmatic condition by stimulating ciliary beating and also by suppressing airway inflammation.
authors.affiliation: Department of Pharmacotherapy, Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Narumoto
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Niikura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ishii
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Morihara
authors.forename: Saki
authors.initials: S
authors.lastname: Okashiro
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakahari
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Matsumura
authors.forename: Chikao
authors.initials: C
authors.lastname: Shimamoto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Moriwaki
authors.forename: Hidemi
authors.initials: H
authors.lastname: Misawa
authors.forename: Naohide
authors.initials: N
authors.lastname: Yamashita
authors.forename: Takahide
authors.initials: T
authors.lastname: Nagase
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kawashima
authors.forename: Naomi
authors.initials: N
authors.lastname: Yamashita
mesh_terms: D000950:Antigens, Ly / Q000494:pharmacology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D009079:Mucociliary Clearance / Q000187:drug effects / Q000276:immunology*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology*; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology
chemical_list: D000950:Antigens, Ly; C545249:SLURP-1 protein, mouse; D014568:Urokinase-Type Plasminogen Activator
keywords: Acetylcholine; Asthma; Bronchial epithelial cells; Ciliary beating; Mucociliary transport; Nicotinic receptors