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Expression of SLURP‐1, an endogenous α7 nicotinic acetylcholine receptor allosteric ligand, in murine bronchial epithelial cells
Author(s) -
Horiguchi Kazuhide,
Horiguchi Satomi,
Yamashita Naomi,
Irie Kaoru,
Masuda Junya,
TakanoOhmuro Hiromi,
Himi Toshiyuki,
Miyazawa Mai,
Moriwaki Yasuhiro,
Okuda Takashi,
Misawa Hidemi,
Ozaki Hiroshi,
Kawashima Koichiro
Publication year - 2009
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22102
Subject(s) - receptor , in situ hybridization , urokinase receptor , biology , nicotinic agonist , acetylcholine receptor , chemistry , microbiology and biotechnology , gene expression , biochemistry , gene
Mammalian secreted lymphocyte antigen‐6/urokinase‐type plasminogen activator receptor‐related peptide‐1 (SLURP‐1) is a positive allosteric ligand for α7 nicotinic acetylcholine (ACh) receptors (α7 nAChRs) that potentiates responses to ACh and elicits proapoptotic activity in human keratinocytes. Mutations in the gene encoding SLURP‐1 have been detected in patients with Mal de Meleda, a rare autosomal recessive skin disorder characterized by transgressive palmoplantar keratoderma. On the basis of these findings, SLURP‐1 is postulated to be involved in regulating tumor necrosis factor‐α (TNF‐α) release from keratinocytes and macrophages via α7 nAChR‐mediated pathways. In the present study, we assessed SLURP‐1 expression in lung tissue from C57BL/6J mice to investigate the functions of SLURP‐1 in pulmonary physiology and pathology. Immunohistochemical and in situ hybridization analyses revealed expression of SLURP‐1 protein and mRNA, respectively, exclusively in ciliated bronchial epithelial cells. This was supported by Western blotting showing the presence of the 9.5‐kDa SLURP‐1 protein in whole‐lung tissue and trachea. In addition, high‐affinity choline transporter (CHT1) was detected in apical regions of bronchial epithelial cells and in neurons located in the lamina propria of the bronchus, suggesting that bronchial epithelial cells are able to synthesize both SLURP‐1 and ACh. We also observed direct contact between F4/80‐positive macrophages and bronchial epithelial cells and the presence of invading macrophages in close proximity to CHT1‐positive nerve elements. Collectively, these results suggest that SLURP‐1 contributes to the maintenance of bronchial epithelial cell homeostasis and to the regulation of TNF‐α release from macrophages in bronchial tissue. © 2009 Wiley‐Liss, Inc.