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-1β concentrations in the lungs compared with wild-type mice. Exogenous NPY treatment suppressed the development of
bleomycin-induced lung
fibrosis and decreased IL-1β concentrations in the lungs. Moreover, IL-1β neutralization in NPY-deficient mice attenuated the fibrotic changes. NPY decreased IL-1β release, and Y1 receptor antagonists inhibited IL-1β release and induced epithelial-mesenchymal transition in human alveolar epithelial cells. Patients with
idiopathic pulmonary fibrosis had lower NPY and greater IL-1β 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-1β release, and manipulating the
NPY-Y1 receptor axis could be a potential therapeutic strategy for delaying
disease progression.