Neuropeptide Y Antagonizes Development of Pulmonary Fibrosis through IL-1β Inhibition

Neuropeptide Y (NPY), a 36 amino acid residue polypeptide distributed throughout the nervous system, acts on various immune cells in many organs, including the respiratory system. However, little is known about its role in the pathogenesis of pulmonary fibrosis. This study was performed to determine the effects of NPY on pulmonary fibrosis. NPY-deficient and wild-type mice were intratracheally administered bleomycin. Inflammatory cells, cytokine concentrations, and morphological morphometry of the lungs were analyzed. Serum NPY concentrations were also measured in patients with idiopathic pulmonary fibrosis and healthy control subjects. NPY-deficient mice exhibited significantly enhanced pulmonary fibrosis and higher IL-1 beta concentrations in the lungs compared with wild-type mice. Exogenous NPY treatment suppressed the development of bleomycin-induced lung fibrosis and decreased IL-1 beta concentrations in the lungs. Moreover, IL-1 beta neutralization in NPY-deficient mice attenuated the fibrotic changes. NPY decreased IL-1 beta release, and Y1 receptor antagonists inhibited IL-1 beta release and induced epithelial-mesenchymal transition in human alveolar epithelial cells. Patients with idiopathic pulmonary fibrosis had lower NPY and greater IL-1 beta concentrations in the serums compared with healthy control subjects. NPY expression was mainly observed around bronchial epithelial cells in human idiopathic pulmonary fibrosis lungs. These data suggest that NPY plays a protective role against pulmonary fibrosis by suppressing IL-1 beta release, and manipulating the NPY-Y1 receptor axis could be a potential therapeutic strategy for delaying disease progression.

Originally Published in:Itano J, Taniguchi A, Senoo S, Asada N, Gion Y, Egusa Y, Guo L, Oda N, Araki K, Sato Y, Toyooka S, Kiura K, Maeda Y, Miyahara N. Neuropeptide Y Antagonizes Development of Pulmonary Fibrosis through IL-1β Inhibition. Am J Respir Cell Mol Biol. 2022 Dec;67(6):654-665.
DOI: 10.1165/rcmb.2021-0542OC
Copyright © 2022 by the American Thoracic Society
The final publication is available at https://doi.org/10.1165/rcmb.2021-0542OC

This full-text will be available in Dec. 2023.