Expression of SLURP-1, an Endogenous α7 Nicotinic Acetylcholine Receptor Allosteric Ligand, in Murine Bronchial Epithelial Cells
Expression of SLURP-1, an Endogenous α7 Nicotinic Acetylcholine Receptor Allosteric Ligand, in Murine Bronchial Epithelial Cells
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DOI：
10.1002/jnr.22102
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发表时间：
2009-09-01
影响因子：
4.2
通讯作者：
Kawashima, Koichiro
中科院分区：
文献类型：
--
作者：
Horiguchi, Kazuhide;Horiguchi, Satomi;Kawashima, Koichiro
哺乳动物分泌的淋巴细胞抗原-6/尿激酶型纤溶酶原激活物受体相关肽-1（SLURP-1）是α 7烟碱乙酰胆碱（ACh）受体（α 7 nAChRs）的正变构配体，其增强人角质形成细胞对ACh的应答和elevin促凋亡活性。已在患有Mal de Meleda的患者中检测到编码SLURP-1的基因突变，Mal de Meleda是一种罕见的常染色体隐性皮肤病，其特征在于超越性掌跖角化病。基于这些发现，假设SLURP-1参与调节肿瘤坏死因子-α（TNF-α）通过α 7 nAChR介导的途径从角质形成细胞和巨噬细胞释放。在本研究中，我们评估了SLURP-1在C57 BL/6J小鼠肺组织中的表达，以研究SLURP-1在肺生理和病理中的功能。免疫组织化学和原位杂交分析显示，SLURP-1蛋白和mRNA的表达，分别只在纤毛支气管上皮细胞。这得到了蛋白质印迹法的支持，表明在整个肺组织和气管中存在9.5-kDa SLURP-1蛋白。此外，在支气管上皮细胞的顶端区域和位于支气管固有层的神经元中检测到高亲和力胆碱转运蛋白（CHT1），这表明支气管上皮细胞能够合成SLURP-1和ACh。我们还观察到F4/80阳性巨噬细胞和支气管上皮细胞之间的直接接触，以及CHT 1阳性神经元附近存在侵入性巨噬细胞。总的来说，这些结果表明，SLURP-1有助于维持支气管上皮细胞的稳态和调节TNF-α从支气管组织中的巨噬细胞释放。(C)2009 Wiley-Liss，Inc.
Mammalian secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related peptide-1 (SLURP-1) is a positive allosteric ligand for alpha 7 nicotinic acetylcholine (ACh) receptors (alpha 7 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-alpha (TNF-alpha) release from keratinocytes and macrophages via alpha 7 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-alpha release from macrophages in bronchial tissue. (C) 2009 Wiley-Liss, Inc.