Role of the Notch signaling pathway in regulating macrophage polarization in a rat model of fibrotic pigeon breeder’s lung

Abstract

Objectives: The Notch signaling pathway serves as the key regulator of the biological functions of macrophages and may affect the role of macrophages in the development of pigeon breeder’s lung (PBL). This study investigated the possible association of the Notch signaling pathway with the development of fibrotic PBL based on regulation of the polarization of macrophages. Methods: Normal Sprague‒Dawley rats and rats with pigeon exfoliation-induced fibrotic hypersensitivity pneumonitis were selected. DAPT was used to inhibit the Notch signaling pathway in rats, and pulmonary fibrosis, the Notch signaling pathway, macrophage polarization, and dynamic changes in the Th1/Th2 ratio were observed. Results: The levels of key proteins in the Notch signaling pathway were higher in the lung tissues of rats with fibrotic hypersensitivity pneumonitis than in those of normal controls ( p < 0.05). The mRNA expression levels of the M1 marker genes tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) were lower in the lung macrophages of rats with fibrotic hypersensitivity pneumonitis than in those of normal controls. In contrast, the mRNA expression levels of the M2 marker genes Mrc2 and Arg-1 in macrophages were higher in the rats with pneumonitis than in normal controls ( p < 0.05). The bronchoalveolar lavage fluid Th1/Th2 ratio was lower in the fibrotic hypersensitivity pneumonitis group than in the control group, but this trend was reversed DAPT application ( p < 0.05). Conclusion: Notch pathway receptors and ligands activate the inflammatory response of macrophages and participate in the polarization of macrophages to the M1 type. Inhibition of the Notch signaling pathway plays a role in Th1/Th2 imbalance.