| Affiliation: | 1. Department of Pharmacotherapy, Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan;2. Department of Pulmonary Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan;3. Department of Physiology, Osaka Medical College, Osaka, Japan;4. Department of Microbiology and Infection Control, Osaka Medical College, Osaka, Japan;5. Laboratory of Pharmacotherapy I & II, Osaka University of Pharmaceutical Sciences, Osaka, Japan;6. Department of Pharmacology, Faculty of Pharmacy, Keio University, Tokyo, Japan;g Department of Advanced Medical Science, Institute of Medical Science, University of Tokyo, Tokyo, Japan;h Department of Molecular Pharmacology, Kitazato University School of Pharmacy, Tokyo, Japan |
| 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. |
