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

Area of Science:

• Immunology
• Pulmonology
• Neuroendocrinology

Background:

• Neuropeptide Y (NPY) is a widely distributed nervous system peptide influencing immune cells.
• Its role in pulmonary fibrosis pathogenesis remains largely unexplored.
• Pulmonary fibrosis is a progressive lung disease with limited treatment options.

Purpose of the Study:

• To investigate the effects of Neuropeptide Y (NPY) on the development of pulmonary fibrosis.
• To elucidate the underlying mechanisms involving IL-1β and the NPY-Y1 receptor axis.

Main Methods:

• Comparison of pulmonary fibrosis development in NPY-deficient and wild-type mice after bleomycin administration.
• Analysis of inflammatory cells, cytokine levels (IL-1β), and lung morphology.
• Measurement of serum NPY and IL-1β in patients with idiopathic pulmonary fibrosis and healthy controls.
• In vitro studies using human alveolar epithelial cells treated with NPY and Y1 receptor antagonists.

Main Results:

• NPY-deficient mice showed exacerbated pulmonary fibrosis and increased IL-1β levels.
• Exogenous NPY administration suppressed bleomycin-induced lung fibrosis and reduced IL-1β.
• IL-1β neutralization attenuated fibrosis in NPY-deficient mice.
• Patients with idiopathic pulmonary fibrosis exhibited lower serum NPY and higher IL-1β.
• NPY reduced IL-1β release, while Y1 receptor antagonists promoted IL-1β release and epithelial-mesenchymal transition.

Conclusions:

• Neuropeptide Y (NPY) exerts a protective effect against pulmonary fibrosis.
• NPY suppresses pulmonary fibrosis primarily by inhibiting IL-1β release.
• The NPY-Y1 receptor pathway represents a potential therapeutic target for managing pulmonary fibrosis progression.